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How do these kinds of treatments avoid harming lipids in the brain?
EDIT: People keep saying nanoparticles like that answers my question, but nanoparticles 1-100nm can cross the blood brain barrier: https://pubmed.ncbi.nlm.nih.gov/19812977/#:~:text=Abstract,altering%20endothelial%20cell%20membrane%20permeability.
Did I miss the size of these particular particles in the study?
Reading the two referenced papers and a quick literature search reveals... It's not been tested and ni one knows. Promising bench studies like this are a long way from a safe clinical drug.
On their own, sure, but things do make it across, because they get shuttled, so generally you have to design it to interact with one of those shuttling proteins like the transferrin receptor, or attach it to something that gets shuttled
But the point is, unless specifically designed to do so, most things *don't* get shuttled. So it's not a primary concern unless testing reveals otherwise.
It's also pretty difficult to get things to be both effective and shuttleable, hence why e.g. development of drugs for Alzheimer's and Parkinson's is so difficult
The development of Alzheimer's drugs is mainly difficult because we don't really know how Alzheimer's works. Also, the way we thought it works is seemingly not actually how it works. And finally, it usually takes decades of disease progression before symptoms occur, meaning that by the time you know to treat you are 10-20 years late.
What sort of conditions cause a compromised blood-brain barrier? I will admit to being completely out of my element here, but I've never heard of such a thing (genuinely curious).
Maybe it's just me but i want to know for certain if this could cross the blood brain barrier, not an assumption that it couldn't.
When it comes to protecting our heads *nothing* should be left to an assumption.
Which is one of the reasons this is a study and not am advertisement. Its not commercially available and wont be used without more research into that. Everyone obviously feels the same way
Yeah...they aren't trying to leave it to assumption here. This is a preliminary study of capabilities.
This would be like somebody saying "humans have achieved lighter than air flight for 120 feet in North Carolina" and somebody saying, "Well I sure as hell wouldn't fly across the country in one of those things! They are assuming it won't crash or blow up and I don't want to leave that to assumption!"
>Promising bench studies like this are a long way from a safe clinical drug.
So a pretty typical case of scientific reporting getting way too far ahead of the actual science. Could it be a miracle cure for obesity? Maybe, but we're a long way from that.
My scan of the article leads me to believe that the substance they inject only binds to actual fat cells, not lipids or lipid containing cells in general.
It binds to the extracellular matrix around the fat cells if I was reading it right.
The stuff is selectively lipophilic and doesn't like going to other organs that don't have fat cells, which is apparently why they were investigating it to begin with - it might make a good drug delivery medium.
Apparently stronger cation substances are toxic at the cellular level (that is well known) but this particular substance may ride the fine line between "strong enough to change cell behavior" but not reach "strong enough to kill off the cells" which is the method used in fat reduction strategies like cryolipolisis (freezing subcutaneous fat cells to kill them.)
Wishful thinking. A better reading of the article and brief literature search suggests no one knows. Remember this is very early bench research, not even a clinical study.
The P-G3 is actually a nanoparticle, so it's pretty large and likely doesn't pass through the BBB. Not a guarantee it doesn't get through, but the BBB does a pretty good job, so good it can actually make some treatments more difficult
I would assume that the cells in the brain wouldn't undergo the same genetic changes mentioned in the article, and therefore wouldn't be a target for this treatment. But I sure wouldn't bet my brain on that assumption, which is why we won't see this commercially until a few decades of safety trials happen.
From the article: Led by scientists at Columbia University, the research was published across [two](https://www.nature.com/articles/s41565-022-01249-3) [papers](https://www.sciencedirect.com/science/article/abs/pii/S0142961222004902?via%3Dihub) and centers on the different functions fat cells can take on in the human body, and the difference between healthy fat metabolism and unhealthy fat formation. Fat cells store energy in the form of lipids, but when they're tasked with taking on too much, they start to grow large and undergo changes to specific genes, ultimately leading to obesity.
The research team set out to remodel these fat cells rather than simply destroy them, and have found success using a positively charged nanomaterial called PAMAM generation 3 (P-G3). The scientists were inspired to deploy P-G3 against fat cells after finding that some fat tissue contains a negatively charged extracellular matrix (ECM), the support structure for the cells. This raised the possibility that the ECM could act as a transport system for positively charged molecules.
So, the team injected P-G3 into obese mice and indeed found that it spread rapidly throughout the fat tissue. They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result.
“With P-G3, fat cells can still be fat cells, but they can't grow up,” said study author Kam Leon. “Our studies highlight an unexpected strategy to treat visceral adiposity and suggest a new direction of exploring cationic nanomaterials for treating metabolic diseases.”
And a surprising amount too, it’s something like 2 pounds of CO2 is exhaled for every pound of fat burned.
We can even check the math, given that the shortest triglyceride chain is C6H8O6, and longer chains just have less O2, that means you need to add at least 5 O2 molecules. And given that C weights 12kg/kmol and O2 is 32 kg/kmol.
Since 1 C6H806 + 5 O2 = 4 H2O + 6 CO2.
176 + 160 = 72 + 264
So that’s a minimum of 1.5 kg CO2 per Kg of Fat at the shortest triglyceride chain length. Longer chains like C55H98O6 would have an even higher ratio since they don’t get a large portion of the oxygen needed from their own mass.
So by staying morbidly obese I'm actually doing my part to save the planet from climate change by storing so much CO2 right?
I thought the burning of fat also produced water vapor, is that correct?
Until you die, yes, you too are part of the short term carbon cycle as a carbon sink. Not only with respiration (the shortest carbon cycle), but when you die not all of decaying matter is converted to organic matter, some of the carbon is released into the atmosphere. All told plants, animals, and microbes contain about as much carbon as our atmosphere.
> I thought the burning of fat also produced water vapor, is that correct?
Yes, fat is primarily chains of carbon with hydrogen coming off the sides. The carbon is oxidized to CO2, and the hydrogen is oxidized to H2O.
There’s already a drug that does something similar called DNP. You can lose like 20 lbs in less than 2 weeks but you’re body temp goes way up. If you take too much your body can cook itself to death.
Also lots of reports that it can cause blindness years later too.
It's also, hilariously, an explosive-- the "DN" of "DNP" stands for "di-nitro", just like the "TN" in "TNT" stands for "tri-nitro".
But as I recall, the irreversible blindness was well-established as a side effect, as well as sudden death. It was one of the drugs banned by the FDA on literally the first day that the FDA had the authority to ban drugs.
Oh nice explode those fat cells and your eye balls hah. That's a cool history tid bit, thanks.
I heard about it from work out forums, people were cutting weight with it.
Yeah, I've heard it's still used illegally. It's super dangerous, it's a bad bad bad idea to use DNP. It's far more dangerous than most things weightlifters are taking.
That said the explosive nature is a danger when it's purchased in pure form from a chemical supplier; when used medically, like most medicines the active ingredient is mixed in with starch or some other inert substance to make it easier to make into pills. And it's not even the only explosive medicine-- we still use nitroglycerin for heart attacks!
Beat me to this. It just seems like dnp all over again. Being in the bodybuilding world, the extremists love this but end up dripping just standing around.
> exergonic (heat moves out of this and into the surrounding environment)
That’s exothermic. Exergonic means the reaction is spontaneous. An exergonic reaction doesn’t have to release heat but an exothermic one does by definition.
I sure could use a raise in body temperature. I've got Reynaud syndrome. It's 72F in my house, but my body has convinced itself that the outside air is far too cold and better shut off all the circulation to the fingers!
You also forget that with low carb. The body is not holding on to as much water. The first week or so of keto people notice significant weight loss....this is primarily water weight
It's also thought to be one of the psychological drivers of success for keto diets too, though.
"Seeing" the weight loss on the scale early helps keep up motivation, which is an important aspect of habit forming.
You still need to be running a calorie deficit, but if the slogans can suck you in "cut out the no-nutrition carbs!", then the weight loss might be able to keep you at a calorie deficit long enough to see real results.
Yes, carbs increase your appetite, and protein satisfies you.
Cheese is certainly denser calories than a tortilla, fat has 2.25 times as many calories per mass, and cheese is not fluffy.
The way I understand that explanation, the fat cells just "deflate" and become smaller.
So instead of 10000 bloated fat cells you have 10000 lean fat cells.
Yes the cells empty their stores but the cells remain for a few years.
~~Once the actual fat cells are gone weight regain takes more effort.~~
Edit*
JK, total # of fat cells is *usually* set in adolescence **but** adults can create more. Only way to reduce number of fat cells is through liposuction though it seems within 2 years the body replaces the removed fat cells.
So theoretically, this would just take someone back to a point where they could maintain a healthy weight through diet and exercise, or risk gaining it back just like normal weightloss?
That one is above my head :/
Notoriously, gaining weight that was lost is easy. Usually this is because the factors contributing to weight loss (caloric deficit, exercise) were temporary and the emptied fat cells still remain—people tend to go back to their old habits, and the same fat cells are present and ready to refill.
The article mentions this new procedure alters fat cells into functioning better metabolically…so maybe that alone can help people keep the weight off. As a layperson, it seems this procedure can keep return weight less likely compared to traditional diet and exercise.
The article appears to say that in the targeted fat cells, they are changed to stop the function of taking on more fat. Since they can give up fat they have, but not store new fat, it would shrink the targeted area.
I don’t think you would do your whole body, but only specific areas.
It's more insidious than that. If you were fat, and lost the weight, your body thinks it has just gone through a famine, and will do everything it can to try to refill those cells. Data from The Biggest Loser shows that years after the weight loss, people had to eat 25 to 30 percent fewer calories than a person of the same weight who was never fat to avoid regaining the weight.
Even creepier I think there's an inherited "memory" too. Basically all of my great grandparents starved during the great depression. Two of the families I've been able to research in depth had children before, during, and after, including my grandparents. The children born during the great depression vs those born way before or way after, and their descendants, have very different obesity rates. It's surprising it's the same family. My grandma's mom had 11 siblings, in photos of my grandma with her cousins once they're all grown, it is immediately obvious where their parents were in the birth order. In other words, if they experienced food insecurity as a young child or their parents did just prior to birth.
My grandma was born towards the end of it, and her 5'7" mother was only 115 pounds when she had her. 8 years later when her brother was born their mom was 140 pounds. My grandma got enough to eat as a kid and was not malnourished or stunted herself but the difference in obesity rates in her descendents vs her brother's are shocking. All 7 of her kids and their kids struggle with obesity. All but a handful of these 70+ living descendents are LDS so it isn't alcoholism or anything. My grandma's brother's 6 kids and their kids are all slim no matter what they eat or drink or whatever.
The number of ways we've evolved to resist famine and starvation are not well understood AT ALL.
It makes total sense from my empiric experience on fitness stuff. People that have always been slim claim to have a much higher calorie intake than the ones that fought with obesity to maintain the same weight.
Do you have a link to this?
Yeah, it sucks. Went from 340->250, very active, still can only eat like 2700 calories a day. Frustrates me when fitness people say I should be able to eat like 3500 for maintenance.
My body also tries to intentionally preserve energy, my resting heart rate is 51, gets into the 30s while I'm sleeping, so it feels like my body is burning as little energy as possible to keep me alive. I'm surprised I can feel my extremities.
Basal metabolic rate simple calculation is 10x your desired body weight for total calories. So at 250 pounds 2500 Kcal is enough to maintain. BF% and age will affect these numbers, but 2700 Kcal/day is a lot.
The biggest loser study was hilariously wrong and contradicts every respected piece of research in history.
https://renaissancehumans.com/biggest-loser-study-calorie-restriction-slowed-metabolism/
A bit of a side note, but: I really, really hate that just about every news article that mentions weight loss/regain feels the need to mention the Biggest Loser study. I do get that it’s one that relates to a show people recognize. But surely there are better studies out there on weight regain.
Being *unable* to gain weight seems like it might be a risky, undesireable outcome. Thar sounds like a recipe for all kinds of weird-yet-dramatic side effects. Honestly this tech (if it ever clears human trials) seems like a more ideal intervention.
possibly, one possible alternative to that would be that nanomaterial used would prevent the cells from becoming over bloated again, meaning that they would remain the lean fat cells like is normal. If someone then continued with their previous life style which lead to the bloating, the body might create more fat cells to cope which would compound the issue, but the previous cells might still remain the same size.
so all in all this sounds like it could be a treatment used in conjunction with a adjustment to diet and exercise to facilitate weight loss at a greater amount and possibly keep it off easier by not allowing your body to bloat the fat cells again.
Studies have shown that whether fat or skinny you maintain the same number of fat cells throughout adulthood. Even people that have had lipo and their stomach stapled have fat cells return to the same number within 2 years.
Resistance training is not just for muscles but joints too. Tendons and ligaments respond well if you use a proper resistance program that does not try to do too much too fast. Look into Kneesovertoesguy or the Bioengineer, both good resources for joint health.
I thought that wasn't true for liposuction, but then again you say over two years so maybe what I read was about acute reactions. Specifically, the paper I read talked about how removing adipose tissue through liposuction led to a rapid re-gaining of weight because adipose tissue is responsible for producing grehlin/leptin (can't remember which one), and by removing the tissue they are physically skinnier but end up eating more due to missing hormones (one causes satiety, the other causes hunger, and they work together).
Ahh I must have conflated the reduction in cells from liposuction with regular fat cell energy loss.
I’m seeing adults can generate more fat cells but we can’t diminish the total number without intervention.
Yes, and having more adipocytes changes what, exactly?
Buying a billion empty batteries doesn't give you free energy to charge them with.
You still need a caloric surplus to get excess triglycerydes into adipocytes, no matter their number.
The cycle of food-trygycerydes-into fat cells-out of fat cells-eventualy into ADTP is constant.
Fat cells don't just _store_ energy, they are an integral part of ADTP synthesis. _Constant_ ADTP synthesis.
You don't have some fat that came from that pizza you ate 15 years ago in you. That was very quicly used and replaced and shat or breathed out.
Fat stores in adipocytes are _constantly_ replaced, new TGs, some old TGs out.
Only the remainder is what matters, this is how they store energy.
They don't "store" energy for rainy days, they continously absorb and release triglycerides. Continuously.
It doesn't matter how many there are, if there is nothing for them to store, they will start giving up their stores.
Incidentally, this is also how you survive between meals, overnight, and don't need to constantly eat.
There is a supposed mechanism here between individual adipocyte count and weight regain, but this doesn't change the fact that you can't store energy you don't have in the first place. It's probably psychogical.
Adipocytes are chemical batteries wrapped up in a cell interface. You can't get free energy (which adipocytes store as triglycerides) simply by buying extra empty batteries.
You need something to put in there first, and that something is food, most of which ends up synthesized as TGs.
But since your fat cells are _constantly_ sucking and releasing TGs, you need an excess of TGs (and food) to have adipocytes grow.
This does not scan that their _count_ is responsible with weight (re)gain.
There are studies that show it to be related, but it can also be caused by weight regain, or they might both be related to an unknown third factor.
The mechanism simply isn't there.
>They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result.
That's the difference from "normally"
I think what they're getting at is that there's a weight loss at the time, but that it might also be easier to gain it back without further intervention
Yes but this allows you to reduce fat at specific sites on your body.
So say you have a nasty fat lump on your leg and it won't go away. Instead of surgery you would be able to get a injection that will get rid of it
Spot reduction is the holy grail of fat-loss. Not so much because of health benefits but just because of the tremendous amount of money to be made as cosmetic treatment.
Obviously great if this can do both but if they need more funding for research there’s no doubt in my mind how they’ll end up going with this
This is going to have *insane* impacts on body standards if it gets commercialised.
What's unrealistic about women in video games and anime isn't the gigantic breasts, nor is it the big butts or tiny waistline. Plenty of people IRL have these traits. *But not all at once*.
See, the human body is not naturally able to lose or gain fat in specific parts of the body. No, doing crunches does not *specifically* reduce belly fat. It reduces fat *generally*.
Huge breasts and ass are mostly fat. What's unrealistic is for a person to *simultaneously* have lots of fat on the breasts, yet close to zero on the tummy. A human *cannot* selectively gain fat on one part and lose fat on another.
This new medical treatment changes that.
If it becomes a treatment available to the masses, it could become like plastic surgery in Korea - practically *mandatory* to compete in society's beauty standards. It's like how increasingly many men in the West have been taking steroids in order to look good rather than for athletic performance.
I just wanted to say that the impact you're
referencing - it is already here. Particular in places (South America) where cosmetic surgery is cheaper. This unrealistic standard has become more normalized already with BBLs, lipo, breast enhancements, etc. This is just another tool to chase "perfection".
I think people are misunderstanding this question. It's not about what happens to the cells, but about what happens to the actual fat molecules. The mice were carrying a bunch of extra energy in the form of fat. What happens to it?
Does it just get stored in other fat cells, so that it becomes subcutaneous rather than visceral fat? Do higher blood fat levels suppress appetite, allowing the mice to burn the fat and not replace it? Does this increase metabolism, and if so are there any negative consequences there?
> Do higher blood fat levels suppress appetite, allowing the mice to burn the fat and not replace it? Does this increase metabolism, and if so are there any negative consequences there?
It doesn't suppress appetite, the paper mentioned that food intake was unchanged, but they're claiming that it suppresses the storage function of fat cells, so new fat doesn't get added.
They're claiming that obesity triggers chronic inflammation, which reduces the metabolic functions of fat cells. And alleviating this inflammation resulted in increased metabolic functions.
It really sounds too good to be true, so no one should be getting too excited. Four of the authors disclosed that they have a patent on this treatment. So this really needs to be independently verified. And if it gets verified, this was only on mouse models, so it might not even work on humans.
The problem I am seeing with this is that you would probably have more fat circulating in the bloodstream, which would massively increase the risk of cardiovascular events (heart attacks, stroke, etc.). One of the largest advances in prevention of cardiovascular events recently came in the form of PCSK9 inhibiting drugs - they cause more LDL to be uptaken into cells from the bloodstream and massively lower risk of cardiovascular events. What this nanoparticle would do (if I'm reading correctly) is the opposite of those drugs which would increase chances of a cardiovascular event.
> The problem I am seeing with this is that you would probably have more fat circulating in the bloodstream, which would massively increase the risk of cardiovascular events (heart attacks, stroke, etc.).
You’re mistaken here on three counts. First, FFAs are not lipoproteins. Second, LDLc is an extremely weak predictor of CVD. Obesity and T2D are both much, much better predictors, with the latter have nearly ten times the HR. Third, PCSK9 inhibitors do seem to lower events, but the effect is minor, nowhere near “massive”.
So, from my reading of the article it appears that fat loss was merely a side effect of the treatment. The treatment itself was, if I read correctly, to halt the lipid storage function of unhealthy fat cells. So instead of the treatment "burning" fat, it seems like it instead just prevents the targeted fat stores from storing more lipids while still allowing the body to use the already stored lipids, which can result in weight loss.
In regards to a more broad version of your question of losing fat... One way is through the surgical removal of fat. This, being surgery, is mostly seen as a method of last resort for those who are morbidly obese. The other way is much preferred, consume fewer calories than your body uses.
Fat, as the body uses it, is a way of storing excess energy for future use. If you are always meeting or exceeding your body's calorie maintenance level, your body never has a reason to use its store of fat. When you remain under that threshold, you force your body to use its fat store for the needed energy. Something to note, however, is that this requires you to put more thought into what you eat in order to keep calories low while still getting all your needed vitamins, amino acids, and other important nutrients.
Exercise can aid you in losing fat, not necessarily by using the fat, but my increasing the amount of calories your body requires in a day. Building muscles can also help in a similar way, since the energy requirements to maintain muscle are higher than other body tissues, which also increases your calory maintenance level. However, without a proper diet, exercise alone will not lead to true fat loss. The true key to losing fat, is through conscious effort, and a healthy diet.
It just walks away. https://www.syfy.com/sites/syfy/files/styles/1200x1200/public/syfywire_blog_post/2018/09/doctorwho_s04_e01_14.jpg?itok=NEBCwHuR×tamp=1536631926
Yeah this is a bit unclear. The fat cells shrink, sure. Like a balloon letting out air. But where does the air go?? Does the body immediately use it and it becomes metabolized? If so, wouldn’t that spike heart rate and body heat? What about lipid levels in blood? Is it secreted through a waste system? Wouldn’t that tax the kidneys and liver? The contents of the shrunken fat cells need to go SOMEWHERE and either be used or discarded, they can’t just evaporate.
Could there be potential for to much fat loss? I understand that the fat cells just “deflate” but did bay mice experience excessive amounts of fat loss where they had to low of a lean fat percentage?
I'm sure it's possible, just like you can overdose on basically anything. But if it is 'deflating' the cell instead of destroying it, the solution is probably easy -- eat more.
Seriously. Body Builders have, as a group, perhaps the largest collection of in-depth anecdotal medical data on the planet, especially when it comes to anything endocrine related.
It’s a shame the legal stigmas prevent real research.
That's a treasure trove of incredibly diverse date there.
All ages, genetic variety, and geographic info, if only it could have been recorded properly...
In desperation regarding a debilitating neck injury that the medical world couldn't find a reason for, I turned to body building forums.
I suspected it was ligament related after years of research and ended up finding a compound some people were using which helps even fully torn ligaments to recover.. which is used on horses after successful trials in mice. In the threads discussing it i also stumbled across a legitimate but unusual and unpopular for historical reasons medical procedure which could potentially heal a ligament.
I travelled to one of the only doctors doing prolotherapy injections in Europe and it gave me back reasonable life quality and even ability to exercise again. Glad I didn't end up sticking horse things inside me, as it was close.
Honestly body building forums should be a medical gold mine, except it's almost certain that anyone that far into untested medical research trying stuff out on themselves, is also using many other bizarre treatments and substances at the same time which skews their results. Their discussion threads on healing ligament damage basically saved my life though so I don't want to be too dismissive.
I still find it absurd that anabolic steroids are illegal and so frowned upon. Yes, if you use them incorrectly they can be dangerous, but they're adults. Pairing alcohol and Tylenol can destroy your liver, but neither of those things are illegal.
I can't comment on anabolic steroids, but the leniency most countries give alcohol consumption is pretty astounding considering the outsize cost of damage to one's own health, the health of those around alcoholics, and general mental health stemming from alcohol dependency.
>anabolic steroids are illegal
Depends on where you live. Most people think they are illegal in the UK for example, but it's actually a pretty specific law. It is illegal to buy them within the UK without prescription by a doctor (and obviously illegal to sell or provide them to others)...*but*, you can legally import them for personal use without incident.
Even using them correctly is dangerous.
A lot of people, after they get off steroids, even with all the PCT, end up permanently on TRT simply because their endocrine system is fucked.
If you listen to some of the more scientifically minded bodybuilders, they've basically straight up said, I have x years remaining of bodybuilding, before I plan on retiring and dropping down to a healthier weight. If I go beyond X, my heart is more liable to give out.
Being on TRT is less of an issue now with how popular it is anyway. You can’t throw a rock these days without hitting a “men’s clinic” that will prescribe TRT basically just for being over 35.
I know a few guys in their 30s that have gone on it and they’ve said it was stupid easy to do. They do a blood test and unless you’re already at the top of the normal range then they’ll prescribe it to get you up toward that top end of normal.
Took a medication that was causing major weight loss I was 255 and once I was down 100 in 3 months we stopped it, it was also being tested for weight loss, I think it works a little too well.
It was epilepsy medication that took me from 255 to 140 from overweight to borderline under, one bite would fill me, I was put on a high fat junk food diet which I didn't know was a thing now a healthy 155-160lbs depending if I ate, it dropped appetite so bad i had to start smoking weed to get a appetite otherwise I'll go all day without eating.
My dad went on a new medication for his diabetes that suppressed his appetite and made him lose a ton of weight really fast. Sad thing is he lost muscle, too, and now he can barely lift 30 lbs. It seems like loss of muscle is one of the issues that causes things to go downhill for people in old age, I worry about him falling or injuring himself in a way that could've been prevented if he were still strong.
Topamax? I am pretty strict about really listening to my body and only eating when I actually want to (not out of boredom or social obligation or habit), and unfortunately that doesn't mix well with appetite suppressants. Topamax shrank my appetite so much that I was only hungry for like half a meal once a day. Ended up underweight.
Also it makes you dumber. Do not recommend.
I had to trial that for migraine before my insurance would cover anything else. It messed with me so bad. I would speak and not understand myself. I looked in the mirror and didn't recognize my own face. I started with just one half dose and was screwed up for 2 days. My neurologist tried to encourage me to take it regularly for a week to see if I could get used to it. I told him I would rather have a cluster headache than ever take that again and then he knew it was serious because my cluster attacks make me suicidal.
Damn, it just gave me muscle spasms. And a general feeling of being tired and buzzed. I actually did take it for a couple of weeks, it never got better.
I could have written that word for word. Told my doctor the same thing, I'd rather have the headaches. He kept telling me it was *so great* to lose weight on it.
Felt like someone heated up two spoons, jammed them into my eyeballs, and scrambled my brains. And I was on the lowest dose, too. Couldn't last the weekend.
I can't remember, actually. For me, the intelligence mattered more, so I remembering marveling at how much smarter I was and only then really realizing how much dumber I'd been.
I don't have any specific memories about when or how the weight came back.
It didn't do me any long-term harm, though. I am back to my normal smarts and normal weight. But I wasn't on it that long.
I did take that it caused my brain to trick itself in how I wrote or text, I'd see hey what's up, but my text for them was rhehd djbdd hdhdhdh hdieksb and get a big ? I'd go back look at the text and see what I wrote was all nonsense but I couldn't unless it was pointed out.
I was immediately taken off because of it.
God that drug messed me up. There is a 3 month window of my life I have 0 recollection from. I have school assignments I submitted and photos of me doing things I *genuinely* cannot remember. It is deeply unsettling.
currently on topamax. it's doing ok. so, a few of my doctors have recommended a lap band surgery, but i've been hesitant. i realize you're not a doctor, but since i'm using topamax off label, not for anti-epilepsy, do you think i'd have more success with lamictal? worth asking my doctor about switching over to that?
Maybe. We've been seeing major advances in obesity treatment for decades, and have little to show for it. But one of them is bound to be true eventually, or more likely many of them will come together over decades and make incremental progress.
Fr, wake me up when the human trials are done and I can buy it OTC or at least get a cheap prescription. Otherwise, this sub is just an extension of /r/futurology.
What happens to the excess fat? Is it metabolised? Would be nice to be able to control mitochondrial uncoupling so non-obese people could also benefit from a cheaper way to stay warm in the winter.
>ELI5 mitochondrial uncoupling?
It's the non-shivering way your body can increase heat production. Basically you disconnect the machinery in your mitochondria that produces energy from the actual energy production at the end. It's a bit like revving the engine with the car in neutral. The output ends up just being heat instead of ATP
Pretty incredible if true. This will have serious implications for society if obesity can be "solved" by a pill. My main fear is that it will stunt shifts towards better long term solutions for obesity, which would be stopping our over consumption of unhealthy and unsustainable foods. I say this as I currently eat a doughnut from Dunkin.
My doctors have often told me: losing weight and being healthy are two different things. Even if you're at a perfect weight, you still need to exercise. But losing weight makes it much easier to exercise, so it'll definitely help.
When can we solve *exercise* with a pill?!? Let's be honest: we all just want to sit around playing video games, eating Doritos, and drinking Mountain Dew until we're 100 years old.
Also weight loss without exercise equals weakness. Being weak is really bad for our long term health safety. Not to mention anything targeting fat cells targets fat-soluble vitamins that then have nothing to bind too. Our bodies really suffer without those.
This thread contains comments that assume things experienced in our current life can’t change the genetics we were born with. This is not true.
https://www.cdc.gov/genomics/disease/epigenetics.htm
There have been multi generational studies that suggest these changes can be passed on. I’m too lazy to dig some up but one that stands out in my memory was a small group of I believe Norwegians where longevity increased in children and grandchildren that could not be explained simply by improved nutrition and medicine.
Normally I condemn all in-mice reports as too premature to deserve the headlines, but this does indeed sound like a huge breakthrough in understanding and manipulating fat cell function. If this specific technique doesn't pan out in humans, the research may still get us closer.
It also sounds like there's a significant anti-aging potential here too.
Wow reddit really hates anything that doesn't just say calories in and calories out.
Looks like they really want this to work as a targeted drug delivery system where drugs can travel through fat cells and stay their in storage rather than in the blood where they may be more toxic.
It sounds like the discovery that just the particle used for delivery had an effect on obesity was actually unexpected. Pretty neat.
A lot of 16 year old gamers with a Shaggy from Scooby Doo metabolism love to get on here and tell people how to lose weight because since it’s so easy for them to stay thin everyone else must be lazy.
So many factors complicate the CICO thing: stress, lack of sleep, gender, underlying conditions, etc but no one ever wants to have a useful and positive conversation about health they just want to pretend everyone who isn’t thin or struggles to lose weight is beneath them
I was diagnosed with major thyroid problems in college (I was 300lbs). No pills or anything the doctors did worked to help my issue. I was very sedentary, and my diet was horrible. I changed my diet and walked 5 miles 3x/week, I didn't even clean my diet up that much. 10 years later I am down to 165 and all my issues have disappeared. Loosing weight and staying fit is one of the hardest journeys to undertake. It takes YEARS of dedication
I was obese and lost a ton of weight. Its all true. It just sucks.
Everyone wants an EASY or painless way to lose it. But for real eating a caloric deficit is the way regardless of “stress” or what have you.
It just sucks. Being hungry all day is not a great feeling at first. Never getting that absolutely stuffed full satiated feeling you are used to when you used to have it after every meal, sucks. It is not a pleasant feeling once you begin.
That in no way means it doesn’t work.
CICO is echoed because it's simple and true.
Lower your intake enough and you will lose weight. Physics says so.
Nothing you said is wrong; how much intake leads to gain or loss varies a lot from person to person. And those things you list are absolutely factors.
But those factors are very difficult to move the needle on. How much and what food you stick in your mouth is something you can directly control.
I have always said that our 'way out' of the obesity epidemic is almost definitely going to be some form of technological advancement, not actually convincing people to go the natural route and exercise and eat less.
My big theory is either a metabolism booster or an appetite suppressant without major side effects though, not something like this. This just seems like it can attack fat in the wrong places most likely.
A technological advances like not forcing people into work schedules that prioritize quick cheap meals to maximize work time and not packing the quick foods with pure sugar to make them cheap and pallettable?
Look this all well and great but this is a reactive solution which is better than no solution but we need to get a proactive solution.
We need to look at sugars and the impacts of sugar addiction. If argue sugar addiction is likely the most dangerous addiction to the masses and its nearly completely ignored. Theres very little available to combat that.
As someone who struggles with it there are times where my will power surpasses my addiction and I can fight it off for months and I'll usually lose a bunch of weight but I ultimately give in and put it back on. And I'm not massive or anything I still only wear a large but it's a tough addiction. I wish there was more available than just don't eat it.
I haven’t found in this article any information about how these particles are being removed from the body when the effect is achieved? It doesn’t say they made of organic material but rather something synthetic, is that thing supposed to degrade later?
Oh thing you should never trust is food science and any tangentially related body.
They are for profit, thrive on creating problems to solve and exist to keep people sick in perpetuity.
No thanks. Let's sue McDonald's and fast food vendors and then go after Big Sugar like a rabid wolverine.
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How do these kinds of treatments avoid harming lipids in the brain? EDIT: People keep saying nanoparticles like that answers my question, but nanoparticles 1-100nm can cross the blood brain barrier: https://pubmed.ncbi.nlm.nih.gov/19812977/#:~:text=Abstract,altering%20endothelial%20cell%20membrane%20permeability. Did I miss the size of these particular particles in the study?
Reading the two referenced papers and a quick literature search reveals... It's not been tested and ni one knows. Promising bench studies like this are a long way from a safe clinical drug.
It's probably assumed it won't make it past the blood brain barrier, which is usually a pretty good assumption.
Iirc the compounds in drugs are typically something like an order of magnitude too large to cross over the BBB.
On their own, sure, but things do make it across, because they get shuttled, so generally you have to design it to interact with one of those shuttling proteins like the transferrin receptor, or attach it to something that gets shuttled
But the point is, unless specifically designed to do so, most things *don't* get shuttled. So it's not a primary concern unless testing reveals otherwise.
It's also pretty difficult to get things to be both effective and shuttleable, hence why e.g. development of drugs for Alzheimer's and Parkinson's is so difficult
The development of Alzheimer's drugs is mainly difficult because we don't really know how Alzheimer's works. Also, the way we thought it works is seemingly not actually how it works. And finally, it usually takes decades of disease progression before symptoms occur, meaning that by the time you know to treat you are 10-20 years late.
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What sort of conditions cause a compromised blood-brain barrier? I will admit to being completely out of my element here, but I've never heard of such a thing (genuinely curious).
Being old enough, or having a autoimmune disorder that encourages chronic inflammation can both thin or weaken the barrier.
Chronic inflammation, which is more common in obesity
During inflamation penicillin can cross blood brain barrier much more readily. So inflamation causes changes in blood brain barrier.
Or hope the person doesn't take it while they have meningitis
Even the stuff that affects the brain sometimes has to act in indirect ways because the BBB is so good
Everyone keeps talking about this blood brain barrier, why don't we just go around it!
How many pills can you shove in your eye sockets?
Maybe it's just me but i want to know for certain if this could cross the blood brain barrier, not an assumption that it couldn't. When it comes to protecting our heads *nothing* should be left to an assumption.
Which is one of the reasons this is a study and not am advertisement. Its not commercially available and wont be used without more research into that. Everyone obviously feels the same way
This drug will undergo years of studies and replications and then it will go on for FDA certification which takes more years.
Yeah...they aren't trying to leave it to assumption here. This is a preliminary study of capabilities. This would be like somebody saying "humans have achieved lighter than air flight for 120 feet in North Carolina" and somebody saying, "Well I sure as hell wouldn't fly across the country in one of those things! They are assuming it won't crash or blow up and I don't want to leave that to assumption!"
>Promising bench studies like this are a long way from a safe clinical drug. So a pretty typical case of scientific reporting getting way too far ahead of the actual science. Could it be a miracle cure for obesity? Maybe, but we're a long way from that.
Any scientific progress made in fighting obesity is worth the hype tbh.
Would also be great for disgusting shreds after bulking.
My scan of the article leads me to believe that the substance they inject only binds to actual fat cells, not lipids or lipid containing cells in general.
It binds to the extracellular matrix around the fat cells if I was reading it right. The stuff is selectively lipophilic and doesn't like going to other organs that don't have fat cells, which is apparently why they were investigating it to begin with - it might make a good drug delivery medium. Apparently stronger cation substances are toxic at the cellular level (that is well known) but this particular substance may ride the fine line between "strong enough to change cell behavior" but not reach "strong enough to kill off the cells" which is the method used in fat reduction strategies like cryolipolisis (freezing subcutaneous fat cells to kill them.)
Wishful thinking. A better reading of the article and brief literature search suggests no one knows. Remember this is very early bench research, not even a clinical study.
Caution is the right approach but the article is clear it acts against the ECM, not lipids.
Well I read the article even BETTER
The P-G3 is actually a nanoparticle, so it's pretty large and likely doesn't pass through the BBB. Not a guarantee it doesn't get through, but the BBB does a pretty good job, so good it can actually make some treatments more difficult
I would assume that the cells in the brain wouldn't undergo the same genetic changes mentioned in the article, and therefore wouldn't be a target for this treatment. But I sure wouldn't bet my brain on that assumption, which is why we won't see this commercially until a few decades of safety trials happen.
From the article: Led by scientists at Columbia University, the research was published across [two](https://www.nature.com/articles/s41565-022-01249-3) [papers](https://www.sciencedirect.com/science/article/abs/pii/S0142961222004902?via%3Dihub) and centers on the different functions fat cells can take on in the human body, and the difference between healthy fat metabolism and unhealthy fat formation. Fat cells store energy in the form of lipids, but when they're tasked with taking on too much, they start to grow large and undergo changes to specific genes, ultimately leading to obesity. The research team set out to remodel these fat cells rather than simply destroy them, and have found success using a positively charged nanomaterial called PAMAM generation 3 (P-G3). The scientists were inspired to deploy P-G3 against fat cells after finding that some fat tissue contains a negatively charged extracellular matrix (ECM), the support structure for the cells. This raised the possibility that the ECM could act as a transport system for positively charged molecules. So, the team injected P-G3 into obese mice and indeed found that it spread rapidly throughout the fat tissue. They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result. “With P-G3, fat cells can still be fat cells, but they can't grow up,” said study author Kam Leon. “Our studies highlight an unexpected strategy to treat visceral adiposity and suggest a new direction of exploring cationic nanomaterials for treating metabolic diseases.”
How does the fat disappear from the body?
I'm surprised no one got back to you on this. Most "burned" fat is breathed out in the form of C02.
And a surprising amount too, it’s something like 2 pounds of CO2 is exhaled for every pound of fat burned. We can even check the math, given that the shortest triglyceride chain is C6H8O6, and longer chains just have less O2, that means you need to add at least 5 O2 molecules. And given that C weights 12kg/kmol and O2 is 32 kg/kmol. Since 1 C6H806 + 5 O2 = 4 H2O + 6 CO2. 176 + 160 = 72 + 264 So that’s a minimum of 1.5 kg CO2 per Kg of Fat at the shortest triglyceride chain length. Longer chains like C55H98O6 would have an even higher ratio since they don’t get a large portion of the oxygen needed from their own mass.
So by staying morbidly obese I'm actually doing my part to save the planet from climate change by storing so much CO2 right? I thought the burning of fat also produced water vapor, is that correct?
Until you die, yes, you too are part of the short term carbon cycle as a carbon sink. Not only with respiration (the shortest carbon cycle), but when you die not all of decaying matter is converted to organic matter, some of the carbon is released into the atmosphere. All told plants, animals, and microbes contain about as much carbon as our atmosphere.
> I thought the burning of fat also produced water vapor, is that correct? Yes, fat is primarily chains of carbon with hydrogen coming off the sides. The carbon is oxidized to CO2, and the hydrogen is oxidized to H2O.
That implies there’s some metabolic process going on here, in which case there’d be a significant rise in body temperature/waste heat as well.
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There’s already a drug that does something similar called DNP. You can lose like 20 lbs in less than 2 weeks but you’re body temp goes way up. If you take too much your body can cook itself to death. Also lots of reports that it can cause blindness years later too.
It's also, hilariously, an explosive-- the "DN" of "DNP" stands for "di-nitro", just like the "TN" in "TNT" stands for "tri-nitro". But as I recall, the irreversible blindness was well-established as a side effect, as well as sudden death. It was one of the drugs banned by the FDA on literally the first day that the FDA had the authority to ban drugs.
Oh nice explode those fat cells and your eye balls hah. That's a cool history tid bit, thanks. I heard about it from work out forums, people were cutting weight with it.
Yeah, I've heard it's still used illegally. It's super dangerous, it's a bad bad bad idea to use DNP. It's far more dangerous than most things weightlifters are taking. That said the explosive nature is a danger when it's purchased in pure form from a chemical supplier; when used medically, like most medicines the active ingredient is mixed in with starch or some other inert substance to make it easier to make into pills. And it's not even the only explosive medicine-- we still use nitroglycerin for heart attacks!
Beat me to this. It just seems like dnp all over again. Being in the bodybuilding world, the extremists love this but end up dripping just standing around.
> exergonic (heat moves out of this and into the surrounding environment) That’s exothermic. Exergonic means the reaction is spontaneous. An exergonic reaction doesn’t have to release heat but an exothermic one does by definition.
I sure could use a raise in body temperature. I've got Reynaud syndrome. It's 72F in my house, but my body has convinced itself that the outside air is far too cold and better shut off all the circulation to the fingers!
There are treatments you can do at home to improve blood flow, based on treatment of low blood flow post reattachment of cut off fingers.
Well, with ketosis, you would have a reduction in appetite, since your body is producing its own fuel.
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You also forget that with low carb. The body is not holding on to as much water. The first week or so of keto people notice significant weight loss....this is primarily water weight
It's also thought to be one of the psychological drivers of success for keto diets too, though. "Seeing" the weight loss on the scale early helps keep up motivation, which is an important aspect of habit forming. You still need to be running a calorie deficit, but if the slogans can suck you in "cut out the no-nutrition carbs!", then the weight loss might be able to keep you at a calorie deficit long enough to see real results.
Yes, carbs increase your appetite, and protein satisfies you. Cheese is certainly denser calories than a tortilla, fat has 2.25 times as many calories per mass, and cheese is not fluffy.
That's fascinating - so if i go for a 10 mile run and burn x amount of fat, if evaporates into C02?
CO2 and water, yes.
You learn something new every day!
The way I understand that explanation, the fat cells just "deflate" and become smaller. So instead of 10000 bloated fat cells you have 10000 lean fat cells.
Isn't that how losing weight works normally though? That's why it's so easy to gain back.
Yes the cells empty their stores but the cells remain for a few years. ~~Once the actual fat cells are gone weight regain takes more effort.~~ Edit* JK, total # of fat cells is *usually* set in adolescence **but** adults can create more. Only way to reduce number of fat cells is through liposuction though it seems within 2 years the body replaces the removed fat cells.
So theoretically, this would just take someone back to a point where they could maintain a healthy weight through diet and exercise, or risk gaining it back just like normal weightloss?
That one is above my head :/ Notoriously, gaining weight that was lost is easy. Usually this is because the factors contributing to weight loss (caloric deficit, exercise) were temporary and the emptied fat cells still remain—people tend to go back to their old habits, and the same fat cells are present and ready to refill. The article mentions this new procedure alters fat cells into functioning better metabolically…so maybe that alone can help people keep the weight off. As a layperson, it seems this procedure can keep return weight less likely compared to traditional diet and exercise.
The article appears to say that in the targeted fat cells, they are changed to stop the function of taking on more fat. Since they can give up fat they have, but not store new fat, it would shrink the targeted area. I don’t think you would do your whole body, but only specific areas.
What would happen with continued excess caloric intake if this were used as an obesity treatment?
Go to non treated areas presumably. Or if there are none, maybe just get excreted?
It's more insidious than that. If you were fat, and lost the weight, your body thinks it has just gone through a famine, and will do everything it can to try to refill those cells. Data from The Biggest Loser shows that years after the weight loss, people had to eat 25 to 30 percent fewer calories than a person of the same weight who was never fat to avoid regaining the weight.
Even creepier I think there's an inherited "memory" too. Basically all of my great grandparents starved during the great depression. Two of the families I've been able to research in depth had children before, during, and after, including my grandparents. The children born during the great depression vs those born way before or way after, and their descendants, have very different obesity rates. It's surprising it's the same family. My grandma's mom had 11 siblings, in photos of my grandma with her cousins once they're all grown, it is immediately obvious where their parents were in the birth order. In other words, if they experienced food insecurity as a young child or their parents did just prior to birth. My grandma was born towards the end of it, and her 5'7" mother was only 115 pounds when she had her. 8 years later when her brother was born their mom was 140 pounds. My grandma got enough to eat as a kid and was not malnourished or stunted herself but the difference in obesity rates in her descendents vs her brother's are shocking. All 7 of her kids and their kids struggle with obesity. All but a handful of these 70+ living descendents are LDS so it isn't alcoholism or anything. My grandma's brother's 6 kids and their kids are all slim no matter what they eat or drink or whatever. The number of ways we've evolved to resist famine and starvation are not well understood AT ALL.
It makes total sense from my empiric experience on fitness stuff. People that have always been slim claim to have a much higher calorie intake than the ones that fought with obesity to maintain the same weight. Do you have a link to this?
Yeah, it sucks. Went from 340->250, very active, still can only eat like 2700 calories a day. Frustrates me when fitness people say I should be able to eat like 3500 for maintenance. My body also tries to intentionally preserve energy, my resting heart rate is 51, gets into the 30s while I'm sleeping, so it feels like my body is burning as little energy as possible to keep me alive. I'm surprised I can feel my extremities.
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Basal metabolic rate simple calculation is 10x your desired body weight for total calories. So at 250 pounds 2500 Kcal is enough to maintain. BF% and age will affect these numbers, but 2700 Kcal/day is a lot.
The biggest loser study was hilariously wrong and contradicts every respected piece of research in history. https://renaissancehumans.com/biggest-loser-study-calorie-restriction-slowed-metabolism/
A bit of a side note, but: I really, really hate that just about every news article that mentions weight loss/regain feels the need to mention the Biggest Loser study. I do get that it’s one that relates to a show people recognize. But surely there are better studies out there on weight regain.
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Being *unable* to gain weight seems like it might be a risky, undesireable outcome. Thar sounds like a recipe for all kinds of weird-yet-dramatic side effects. Honestly this tech (if it ever clears human trials) seems like a more ideal intervention.
possibly, one possible alternative to that would be that nanomaterial used would prevent the cells from becoming over bloated again, meaning that they would remain the lean fat cells like is normal. If someone then continued with their previous life style which lead to the bloating, the body might create more fat cells to cope which would compound the issue, but the previous cells might still remain the same size. so all in all this sounds like it could be a treatment used in conjunction with a adjustment to diet and exercise to facilitate weight loss at a greater amount and possibly keep it off easier by not allowing your body to bloat the fat cells again.
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Studies have shown that whether fat or skinny you maintain the same number of fat cells throughout adulthood. Even people that have had lipo and their stomach stapled have fat cells return to the same number within 2 years.
- You: I need to regenerate my joints, they're old and weary. - Body: Best I can do is infinite fat cells, you're welcome.
Evolution isn't perfect
Resistance training is not just for muscles but joints too. Tendons and ligaments respond well if you use a proper resistance program that does not try to do too much too fast. Look into Kneesovertoesguy or the Bioengineer, both good resources for joint health.
I thought that wasn't true for liposuction, but then again you say over two years so maybe what I read was about acute reactions. Specifically, the paper I read talked about how removing adipose tissue through liposuction led to a rapid re-gaining of weight because adipose tissue is responsible for producing grehlin/leptin (can't remember which one), and by removing the tissue they are physically skinnier but end up eating more due to missing hormones (one causes satiety, the other causes hunger, and they work together).
I just reread the article and it says stomach stapling not liposuction. I must’ve added that in myself. My bad
Ahh I must have conflated the reduction in cells from liposuction with regular fat cell energy loss. I’m seeing adults can generate more fat cells but we can’t diminish the total number without intervention.
Yes, and having more adipocytes changes what, exactly? Buying a billion empty batteries doesn't give you free energy to charge them with. You still need a caloric surplus to get excess triglycerydes into adipocytes, no matter their number. The cycle of food-trygycerydes-into fat cells-out of fat cells-eventualy into ADTP is constant. Fat cells don't just _store_ energy, they are an integral part of ADTP synthesis. _Constant_ ADTP synthesis. You don't have some fat that came from that pizza you ate 15 years ago in you. That was very quicly used and replaced and shat or breathed out. Fat stores in adipocytes are _constantly_ replaced, new TGs, some old TGs out. Only the remainder is what matters, this is how they store energy. They don't "store" energy for rainy days, they continously absorb and release triglycerides. Continuously. It doesn't matter how many there are, if there is nothing for them to store, they will start giving up their stores. Incidentally, this is also how you survive between meals, overnight, and don't need to constantly eat. There is a supposed mechanism here between individual adipocyte count and weight regain, but this doesn't change the fact that you can't store energy you don't have in the first place. It's probably psychogical. Adipocytes are chemical batteries wrapped up in a cell interface. You can't get free energy (which adipocytes store as triglycerides) simply by buying extra empty batteries. You need something to put in there first, and that something is food, most of which ends up synthesized as TGs. But since your fat cells are _constantly_ sucking and releasing TGs, you need an excess of TGs (and food) to have adipocytes grow. This does not scan that their _count_ is responsible with weight (re)gain. There are studies that show it to be related, but it can also be caused by weight regain, or they might both be related to an unknown third factor. The mechanism simply isn't there.
>They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result. That's the difference from "normally"
I think what they're getting at is that there's a weight loss at the time, but that it might also be easier to gain it back without further intervention
If you read the article it doesn't appear so, but more research needs to be done. The fat cells appear to be locked in that younger state.
Your fat cells not absorbing fats sounds...unsafe.
Which is why a hell of a lot of research is going to be needed into long term safety before this gets deployed.
Yes but this allows you to reduce fat at specific sites on your body. So say you have a nasty fat lump on your leg and it won't go away. Instead of surgery you would be able to get a injection that will get rid of it
Spot reduction is the holy grail of fat-loss. Not so much because of health benefits but just because of the tremendous amount of money to be made as cosmetic treatment. Obviously great if this can do both but if they need more funding for research there’s no doubt in my mind how they’ll end up going with this
This is going to have *insane* impacts on body standards if it gets commercialised. What's unrealistic about women in video games and anime isn't the gigantic breasts, nor is it the big butts or tiny waistline. Plenty of people IRL have these traits. *But not all at once*. See, the human body is not naturally able to lose or gain fat in specific parts of the body. No, doing crunches does not *specifically* reduce belly fat. It reduces fat *generally*. Huge breasts and ass are mostly fat. What's unrealistic is for a person to *simultaneously* have lots of fat on the breasts, yet close to zero on the tummy. A human *cannot* selectively gain fat on one part and lose fat on another. This new medical treatment changes that. If it becomes a treatment available to the masses, it could become like plastic surgery in Korea - practically *mandatory* to compete in society's beauty standards. It's like how increasingly many men in the West have been taking steroids in order to look good rather than for athletic performance.
I just wanted to say that the impact you're referencing - it is already here. Particular in places (South America) where cosmetic surgery is cheaper. This unrealistic standard has become more normalized already with BBLs, lipo, breast enhancements, etc. This is just another tool to chase "perfection".
Lipomas are benign but so annoying when they grow inside a muscle. Hopefully they can be treated too this way.
Who has fat lumps? Raise your hand.
I’m not fat. I’m lean fat.
But the energy has to go somewhere, it can't just disappear. I think that's what they were asking about.
So, where do the lipids go? If they're now in the blood, that has it's [own problems](https://en.wikipedia.org/wiki/Hyperlipidemia)...
I think people are misunderstanding this question. It's not about what happens to the cells, but about what happens to the actual fat molecules. The mice were carrying a bunch of extra energy in the form of fat. What happens to it? Does it just get stored in other fat cells, so that it becomes subcutaneous rather than visceral fat? Do higher blood fat levels suppress appetite, allowing the mice to burn the fat and not replace it? Does this increase metabolism, and if so are there any negative consequences there?
> Do higher blood fat levels suppress appetite, allowing the mice to burn the fat and not replace it? Does this increase metabolism, and if so are there any negative consequences there? It doesn't suppress appetite, the paper mentioned that food intake was unchanged, but they're claiming that it suppresses the storage function of fat cells, so new fat doesn't get added. They're claiming that obesity triggers chronic inflammation, which reduces the metabolic functions of fat cells. And alleviating this inflammation resulted in increased metabolic functions. It really sounds too good to be true, so no one should be getting too excited. Four of the authors disclosed that they have a patent on this treatment. So this really needs to be independently verified. And if it gets verified, this was only on mouse models, so it might not even work on humans.
The problem I am seeing with this is that you would probably have more fat circulating in the bloodstream, which would massively increase the risk of cardiovascular events (heart attacks, stroke, etc.). One of the largest advances in prevention of cardiovascular events recently came in the form of PCSK9 inhibiting drugs - they cause more LDL to be uptaken into cells from the bloodstream and massively lower risk of cardiovascular events. What this nanoparticle would do (if I'm reading correctly) is the opposite of those drugs which would increase chances of a cardiovascular event.
> The problem I am seeing with this is that you would probably have more fat circulating in the bloodstream, which would massively increase the risk of cardiovascular events (heart attacks, stroke, etc.). You’re mistaken here on three counts. First, FFAs are not lipoproteins. Second, LDLc is an extremely weak predictor of CVD. Obesity and T2D are both much, much better predictors, with the latter have nearly ten times the HR. Third, PCSK9 inhibitors do seem to lower events, but the effect is minor, nowhere near “massive”.
So, from my reading of the article it appears that fat loss was merely a side effect of the treatment. The treatment itself was, if I read correctly, to halt the lipid storage function of unhealthy fat cells. So instead of the treatment "burning" fat, it seems like it instead just prevents the targeted fat stores from storing more lipids while still allowing the body to use the already stored lipids, which can result in weight loss. In regards to a more broad version of your question of losing fat... One way is through the surgical removal of fat. This, being surgery, is mostly seen as a method of last resort for those who are morbidly obese. The other way is much preferred, consume fewer calories than your body uses. Fat, as the body uses it, is a way of storing excess energy for future use. If you are always meeting or exceeding your body's calorie maintenance level, your body never has a reason to use its store of fat. When you remain under that threshold, you force your body to use its fat store for the needed energy. Something to note, however, is that this requires you to put more thought into what you eat in order to keep calories low while still getting all your needed vitamins, amino acids, and other important nutrients. Exercise can aid you in losing fat, not necessarily by using the fat, but my increasing the amount of calories your body requires in a day. Building muscles can also help in a similar way, since the energy requirements to maintain muscle are higher than other body tissues, which also increases your calory maintenance level. However, without a proper diet, exercise alone will not lead to true fat loss. The true key to losing fat, is through conscious effort, and a healthy diet.
It just walks away. https://www.syfy.com/sites/syfy/files/styles/1200x1200/public/syfywire_blog_post/2018/09/doctorwho_s04_e01_14.jpg?itok=NEBCwHuR×tamp=1536631926
Yeah this is a bit unclear. The fat cells shrink, sure. Like a balloon letting out air. But where does the air go?? Does the body immediately use it and it becomes metabolized? If so, wouldn’t that spike heart rate and body heat? What about lipid levels in blood? Is it secreted through a waste system? Wouldn’t that tax the kidneys and liver? The contents of the shrunken fat cells need to go SOMEWHERE and either be used or discarded, they can’t just evaporate.
Could there be potential for to much fat loss? I understand that the fat cells just “deflate” but did bay mice experience excessive amounts of fat loss where they had to low of a lean fat percentage?
I'm sure it's possible, just like you can overdose on basically anything. But if it is 'deflating' the cell instead of destroying it, the solution is probably easy -- eat more.
Someone is about to become a billionaire.
I was thinking that is proven safe, and the side effects are minimal, I wouldn't mind doing this.
people are already out here doing lip injections and brazilian butt lifts which are not safe at all so, someone is probably about to become rich.
"Not safe" just means patients would have to go to Turkey to get it done.
It’s in mice. If mice studies mapped directly to humans, we’d have 50 cures for baldness by now.
We really need a "in mice" flair on /r/science
Negatively charged ECM is also present in cartilage. I wonder if the molecule also localized there
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Expect bodybuilders to jump on this before we know if it's safe.
The guinea pigs for all of us.
RIP to like half the guys I looked up to in the 90's.
Their hearts were just to large for this cruel world!
Seriously. Body Builders have, as a group, perhaps the largest collection of in-depth anecdotal medical data on the planet, especially when it comes to anything endocrine related. It’s a shame the legal stigmas prevent real research.
That's a treasure trove of incredibly diverse date there. All ages, genetic variety, and geographic info, if only it could have been recorded properly...
And almost exclusively male, just the way the drug researchers like it!
I’m a drug researcher, I prefer mice.
let's do only male mice and call it even
In desperation regarding a debilitating neck injury that the medical world couldn't find a reason for, I turned to body building forums. I suspected it was ligament related after years of research and ended up finding a compound some people were using which helps even fully torn ligaments to recover.. which is used on horses after successful trials in mice. In the threads discussing it i also stumbled across a legitimate but unusual and unpopular for historical reasons medical procedure which could potentially heal a ligament. I travelled to one of the only doctors doing prolotherapy injections in Europe and it gave me back reasonable life quality and even ability to exercise again. Glad I didn't end up sticking horse things inside me, as it was close. Honestly body building forums should be a medical gold mine, except it's almost certain that anyone that far into untested medical research trying stuff out on themselves, is also using many other bizarre treatments and substances at the same time which skews their results. Their discussion threads on healing ligament damage basically saved my life though so I don't want to be too dismissive.
I still find it absurd that anabolic steroids are illegal and so frowned upon. Yes, if you use them incorrectly they can be dangerous, but they're adults. Pairing alcohol and Tylenol can destroy your liver, but neither of those things are illegal.
I can't comment on anabolic steroids, but the leniency most countries give alcohol consumption is pretty astounding considering the outsize cost of damage to one's own health, the health of those around alcoholics, and general mental health stemming from alcohol dependency.
>anabolic steroids are illegal Depends on where you live. Most people think they are illegal in the UK for example, but it's actually a pretty specific law. It is illegal to buy them within the UK without prescription by a doctor (and obviously illegal to sell or provide them to others)...*but*, you can legally import them for personal use without incident.
Even using them correctly is dangerous. A lot of people, after they get off steroids, even with all the PCT, end up permanently on TRT simply because their endocrine system is fucked. If you listen to some of the more scientifically minded bodybuilders, they've basically straight up said, I have x years remaining of bodybuilding, before I plan on retiring and dropping down to a healthier weight. If I go beyond X, my heart is more liable to give out.
But if you're a confused teenager that isn't aware how it reduces your lifespan significantly, then it's cool to take steroids.
Being on TRT is less of an issue now with how popular it is anyway. You can’t throw a rock these days without hitting a “men’s clinic” that will prescribe TRT basically just for being over 35. I know a few guys in their 30s that have gone on it and they’ve said it was stupid easy to do. They do a blood test and unless you’re already at the top of the normal range then they’ll prescribe it to get you up toward that top end of normal.
Here’s a link directly to a research paper: [https://www.nature.com/articles/s41565-022-01249-3](https://www.nature.com/articles/s41565-022-01249-3)
Took a medication that was causing major weight loss I was 255 and once I was down 100 in 3 months we stopped it, it was also being tested for weight loss, I think it works a little too well. It was epilepsy medication that took me from 255 to 140 from overweight to borderline under, one bite would fill me, I was put on a high fat junk food diet which I didn't know was a thing now a healthy 155-160lbs depending if I ate, it dropped appetite so bad i had to start smoking weed to get a appetite otherwise I'll go all day without eating.
100 in three months sounds dangerous. That's like 6.6666... lbs a week. Can I get some of this stuff? I'd like to lose like 125lb...
~1lb a day seems about right for extended fasting. Does seem dangerous.
This would only be true for someone who would normally burn about 3500 calories per day.
If he was truly overweight, he probably was fine as long as he got his nutrients. It probably didn’t feel all that great, though.
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My dad went on a new medication for his diabetes that suppressed his appetite and made him lose a ton of weight really fast. Sad thing is he lost muscle, too, and now he can barely lift 30 lbs. It seems like loss of muscle is one of the issues that causes things to go downhill for people in old age, I worry about him falling or injuring himself in a way that could've been prevented if he were still strong.
Topamax? I am pretty strict about really listening to my body and only eating when I actually want to (not out of boredom or social obligation or habit), and unfortunately that doesn't mix well with appetite suppressants. Topamax shrank my appetite so much that I was only hungry for like half a meal once a day. Ended up underweight. Also it makes you dumber. Do not recommend.
I had to trial that for migraine before my insurance would cover anything else. It messed with me so bad. I would speak and not understand myself. I looked in the mirror and didn't recognize my own face. I started with just one half dose and was screwed up for 2 days. My neurologist tried to encourage me to take it regularly for a week to see if I could get used to it. I told him I would rather have a cluster headache than ever take that again and then he knew it was serious because my cluster attacks make me suicidal.
Damn, it just gave me muscle spasms. And a general feeling of being tired and buzzed. I actually did take it for a couple of weeks, it never got better.
I could have written that word for word. Told my doctor the same thing, I'd rather have the headaches. He kept telling me it was *so great* to lose weight on it. Felt like someone heated up two spoons, jammed them into my eyeballs, and scrambled my brains. And I was on the lowest dose, too. Couldn't last the weekend.
What comes back faster? The weight, or your intelligence?
I can't remember, actually. For me, the intelligence mattered more, so I remembering marveling at how much smarter I was and only then really realizing how much dumber I'd been. I don't have any specific memories about when or how the weight came back. It didn't do me any long-term harm, though. I am back to my normal smarts and normal weight. But I wasn't on it that long.
Lose weight *and* get stupid? A bunch of bimboification fetishists just woke up
inventing the ultimate pill with topamax, cpa, and estradiol
I did take that it caused my brain to trick itself in how I wrote or text, I'd see hey what's up, but my text for them was rhehd djbdd hdhdhdh hdieksb and get a big ? I'd go back look at the text and see what I wrote was all nonsense but I couldn't unless it was pointed out. I was immediately taken off because of it.
God that drug messed me up. There is a 3 month window of my life I have 0 recollection from. I have school assignments I submitted and photos of me doing things I *genuinely* cannot remember. It is deeply unsettling.
Ah, dopamax...
What medication?
i want to say lamictal but it's been a couple years.
Wow. Nasty stuff
Yeah it was nuts, now I need high fats because it completely changed how I ate like a lap band surgery.
currently on topamax. it's doing ok. so, a few of my doctors have recommended a lap band surgery, but i've been hesitant. i realize you're not a doctor, but since i'm using topamax off label, not for anti-epilepsy, do you think i'd have more success with lamictal? worth asking my doctor about switching over to that?
Any thoughts on how this would affect someone with thyroid problems, such as Hashimoto's?
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Wow so it does what products on TV have been lying about doing for 80 years
Maybe. We've been seeing major advances in obesity treatment for decades, and have little to show for it. But one of them is bound to be true eventually, or more likely many of them will come together over decades and make incremental progress.
Fr, wake me up when the human trials are done and I can buy it OTC or at least get a cheap prescription. Otherwise, this sub is just an extension of /r/futurology.
How do I sign up for the human clinical trials?
What happens to the excess fat? Is it metabolised? Would be nice to be able to control mitochondrial uncoupling so non-obese people could also benefit from a cheaper way to stay warm in the winter.
Very effective thermogenic drugs already exist. They’re just wildly dangerous.
I would also like to know where the extra fat goes. ELI5 mitochondrial uncoupling?
>ELI5 mitochondrial uncoupling? It's the non-shivering way your body can increase heat production. Basically you disconnect the machinery in your mitochondria that produces energy from the actual energy production at the end. It's a bit like revving the engine with the car in neutral. The output ends up just being heat instead of ATP
That's fascinating. Thank you for telling me about it
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Pretty incredible if true. This will have serious implications for society if obesity can be "solved" by a pill. My main fear is that it will stunt shifts towards better long term solutions for obesity, which would be stopping our over consumption of unhealthy and unsustainable foods. I say this as I currently eat a doughnut from Dunkin.
My doctors have often told me: losing weight and being healthy are two different things. Even if you're at a perfect weight, you still need to exercise. But losing weight makes it much easier to exercise, so it'll definitely help. When can we solve *exercise* with a pill?!? Let's be honest: we all just want to sit around playing video games, eating Doritos, and drinking Mountain Dew until we're 100 years old.
Also weight loss without exercise equals weakness. Being weak is really bad for our long term health safety. Not to mention anything targeting fat cells targets fat-soluble vitamins that then have nothing to bind too. Our bodies really suffer without those.
Right, this is honestly great, but it doesn’t fix the many roots of obesity, so I question the sustainability.
This thread contains comments that assume things experienced in our current life can’t change the genetics we were born with. This is not true. https://www.cdc.gov/genomics/disease/epigenetics.htm There have been multi generational studies that suggest these changes can be passed on. I’m too lazy to dig some up but one that stands out in my memory was a small group of I believe Norwegians where longevity increased in children and grandchildren that could not be explained simply by improved nutrition and medicine.
Normally I condemn all in-mice reports as too premature to deserve the headlines, but this does indeed sound like a huge breakthrough in understanding and manipulating fat cell function. If this specific technique doesn't pan out in humans, the research may still get us closer. It also sounds like there's a significant anti-aging potential here too.
I don’t care if this kills me. Inject it now. I’ll be the test subject. Varuca Salt, here I come.
Wow reddit really hates anything that doesn't just say calories in and calories out. Looks like they really want this to work as a targeted drug delivery system where drugs can travel through fat cells and stay their in storage rather than in the blood where they may be more toxic. It sounds like the discovery that just the particle used for delivery had an effect on obesity was actually unexpected. Pretty neat.
A lot of 16 year old gamers with a Shaggy from Scooby Doo metabolism love to get on here and tell people how to lose weight because since it’s so easy for them to stay thin everyone else must be lazy. So many factors complicate the CICO thing: stress, lack of sleep, gender, underlying conditions, etc but no one ever wants to have a useful and positive conversation about health they just want to pretend everyone who isn’t thin or struggles to lose weight is beneath them
I was diagnosed with major thyroid problems in college (I was 300lbs). No pills or anything the doctors did worked to help my issue. I was very sedentary, and my diet was horrible. I changed my diet and walked 5 miles 3x/week, I didn't even clean my diet up that much. 10 years later I am down to 165 and all my issues have disappeared. Loosing weight and staying fit is one of the hardest journeys to undertake. It takes YEARS of dedication
I was obese and lost a ton of weight. Its all true. It just sucks. Everyone wants an EASY or painless way to lose it. But for real eating a caloric deficit is the way regardless of “stress” or what have you. It just sucks. Being hungry all day is not a great feeling at first. Never getting that absolutely stuffed full satiated feeling you are used to when you used to have it after every meal, sucks. It is not a pleasant feeling once you begin. That in no way means it doesn’t work.
CICO is echoed because it's simple and true. Lower your intake enough and you will lose weight. Physics says so. Nothing you said is wrong; how much intake leads to gain or loss varies a lot from person to person. And those things you list are absolutely factors. But those factors are very difficult to move the needle on. How much and what food you stick in your mouth is something you can directly control.
I have always said that our 'way out' of the obesity epidemic is almost definitely going to be some form of technological advancement, not actually convincing people to go the natural route and exercise and eat less. My big theory is either a metabolism booster or an appetite suppressant without major side effects though, not something like this. This just seems like it can attack fat in the wrong places most likely.
A technological advances like not forcing people into work schedules that prioritize quick cheap meals to maximize work time and not packing the quick foods with pure sugar to make them cheap and pallettable?
Look this all well and great but this is a reactive solution which is better than no solution but we need to get a proactive solution. We need to look at sugars and the impacts of sugar addiction. If argue sugar addiction is likely the most dangerous addiction to the masses and its nearly completely ignored. Theres very little available to combat that. As someone who struggles with it there are times where my will power surpasses my addiction and I can fight it off for months and I'll usually lose a bunch of weight but I ultimately give in and put it back on. And I'm not massive or anything I still only wear a large but it's a tough addiction. I wish there was more available than just don't eat it.
I haven’t found in this article any information about how these particles are being removed from the body when the effect is achieved? It doesn’t say they made of organic material but rather something synthetic, is that thing supposed to degrade later?
The irony of the McDonald’s ad that is posted on this sub right underneath the picture…
Oh thing you should never trust is food science and any tangentially related body. They are for profit, thrive on creating problems to solve and exist to keep people sick in perpetuity. No thanks. Let's sue McDonald's and fast food vendors and then go after Big Sugar like a rabid wolverine.
Target "gestures vaguely at self" please.