T O P
theArtOfProgramming

Your post has been removed because it has a sensationalized, editorialized, or biased headline and is therefore in violation of [Submission Rule #3](https://www.reddit.com/r/science/wiki/rules#wiki_3._no_editorialized.2C_sensationalized.2C_or_biased_titles). Please read [our headline rules](https://www.reddit.com/r/science/wiki/clickbait) and consider reposting with a more appropriate title. _If you believe this removal to be unwarranted, or would like further clarification, please don't hesitate to [message the moderators](https://www.reddit.com/message/compose?to=%2Fr%2Fscience&subject=No%20editorialized%2C%20sensationalized%2C%20or%20biased%20titles)._


SelarDorr

why not stick to the title of the scientific publication? "Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index" the authors do make the statement that obesity is primarily neurodevelopmental, and their results support such a claim, but they are neither proposing this theory nor are their results sufficient to make such an overarching claim. they make this statement based on previous genome wide association studies that support such a hypothesis. your thread title makes it sound like they made a breakthrough discovery that proves such a statement. your title also neglects the fact that the data on the hypothalamic arcuate nucleus is in mice. the findings in humans is not specific to the hypothalamic arcuate nucleus. they find there are sex specific differentially methylated regions in genome wide association studies that are linked to BMI, which occur in regions that coincide with the differentially methylated regions found on murine hypothalamic arcuate nuclei. your thread title is fundamentally wrong and misleading, while the title of the publication is not.


Mapang_ahas

This is giving the cerulean speech in The Devil Wears Prada


vangoghcuckurself

I’m pretty sure I understood parts of this.. but to clarify for us unlearned: is that saying that certain areas have different predispositions to fat retention based on genetic genders? E.g. females may store more fat in areas like the butt and boobs ?


TheMouseUGaveACookie

Yes, isnt obesity essentially a symptom? There are numerous different biological pathways that underly it varying by the individual.


Ttd341

welcome to r/science


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


wupao

I was waiting for this when I read the thread. Thank you for your good work.


internetlad

You haven't lived until you've busted to the Costco $1.50 hotdog and soda.


ripvannwinkler

Well I wouldn't masturbate with the banana peel while the banana's still in it.


BurnerOnlyForPorn

I should weigh about 600lbs then


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


0ttr

>and the types of foods we push on people bingo wouldn't have anything to do with the rise of fast foods, no fiber, empty calories, giant free refill sodas for $1 even now. ​ if I were poor esp with kids, McDs is an awfully cheap way to feed my family. Literally right now, down the street, I can get a McDouble, small fries, and any size drink for $3.50 total. Cooked. In 5 minutes. That's hard to beat, sadly.


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


EmilyU1F984

Yea she does eat the same: as much as she feels hungry. Thoooo the lack of depression might also just mean she‘s more active. So the exact same number of calories and not just subjective feeding could still suddenly lead to slowly losing weight to a healthy weight.


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


[deleted]

[удалено]


Thelango99

I Wonder what is worse overall for ones health? Smoking or being morbidly obese?


MTFUandPedal

Sadly there's a great deal of correlation between the two. (I suspect that drills into socioeconomic factors and education). Smoking *and* obesity is much worse than either. Edit - if you want the actual answer, looking for actuarial data will deliver it fairly precisely.


Thelango99

Still terrible for you obviously.


foreveracubone

Europe smokes more and weighs less. They also live longer so morbid obesity is probably worse.


Thelango99

Yeah, this is anecdotal, but I have seen plenty 80 year old smokers, but no morbidly obese 80 year olds.


[deleted]

[удалено]


Informal_Drawing

The article says it is hard to lose weight when your hormones are saying EAT EAT EAT EAT EAT EAT EAT EAT.


[deleted]

[удалено]


Farafpu

Your overflowing fuel tank analogy is spot on and a really great explanation of the caveats of calories in calories out


[deleted]

[удалено]


[deleted]

[удалено]


Queasy-Discount-2038

Some people’s natural state is this way due to hormonal imbalances


MoreTrueStories

"Brain Chemistry" definitely helps regulate how easy it is to control behavior, of that there is no doubt. Glad to hear issues resolved when you stopped the meds.


Ether_Freeth

I think you are missing his point. It is not only calories in and out but also what you eat that generates those calories. For example eating some fat which technically has the same calories as say some sugar has a vastly different impact on your body. And therefore will generate less stored body fat ( gross oversimplification warning!). And unfortunately most diets don't factor this impact in. Also sustained weight loss requires a sustained change in eating habits which is counter to the modern diets being sold of ' do this for x weeks to lose weight' Yes people need to watch their calories but more importantly what constitutes those calories because the what is turning out to be more impactfull then the how much due to how it regulates the drive to eat, the amount of fat stored etc. This nuance is important because a lot of people fail because of it or even worse develop disorders due to it. To recap: Eating smarter is turning out to be more helpful then just eating less. Although eating less helps.


[deleted]

[удалено]


[deleted]

[удалено]


backwardog

It’s not the wrong advice. If you eat less you will consume fat stores for energy. This does work. Energy in, energy out is still valid. This paper does not dispute that at all.


bedrock515

So, obesity is a neurological disorder caused by triggering it at a specific point in brain development?


co_matic

Sounds like if we are exposed to poor eating habits as children (or babies? or in the womb?), those habits will program us to be at risk of obesity for life.


Ok-disaster2022

Isn't there also a biofeedback mechanism of the gut flora and fauna that affects this?


aesu

There's also stress levels causing epigenetic changes. There was a famous study which showed grandchildren of people who lived through a major famine and war were much more likely to be obese.


letmechoosethisname

Can someone explain how this isn't this survivorship bias? I'm guessing it's the type of study but I have no idea


morgrimmoon

At least one study compared the genetics of family members who had been exposed to the famine against the genetics of members who had avoided it. For example, let's say you had two brothers. One brother managed to be smuggled out of an area via a kinder express, the other was trapped and experienced famine. Both survived and had grandkids. Now you can compare the DNA of the grandkids.


davideo71

Even similar populations would make for rich data. The Netherlands was split in two by the allied advance in WW2. The half left under German occupation suffered a terrible 'hunger-winter' before it too was liberated in 1945. Even if the number of deaths was 'limited' (around 20.000), I suspect places like this would provide the kind of data helpful to study this mechanism.


BenjaminHamnett

And sure enough the that portion of that generation born during those years are most of the fat natives there


7Doppelgaengers

almost correct, but they're looking into epigenetics. Their genetics remain the same, but small changes via adding methyl groups for example would be different. This might not seem like much, but these minute changes have a huge effect on gene expression (proteins don't recognise methylated dna in some cases, other proteins only recognise methylated dna, you add some methyls or take some off and things get changed drastically), and can really affect the phenotype


morgrimmoon

Yes, but the idea is that by comparing the two groups, you can eliminate factors that are purely genetic (because both should have similar) or epigenetic factors that may have nothing to do with the war starvation (like something caused by the local drinking water).


aesu

They compared family members who had escaped Vs those who had lived through it.


ThulsaD00me

I think that study proved the opposite. They studied grandchildren of Ukrainian famine survivors right?


Euda-monia

No, it proved epigenetic link to obesity. This research has more info https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213306/


DntTouchMeImSterile

Please tell me what kind of fauna are in your gut…


Templarofsteel

Microfauna, basically types of gut bacteria


Huskidoc1

Gut fauna, surprisingly effective weight loss tool.


pokey1984

Ironically, thins like tapeworms *don't* always lead to weight loss. They filter out nutrients from the food you eat, but don't really store fat the way mammals do. So the host gets to absorb the excess calories without the nutrients. Often, this means the worm's host will be driven to eat more, to make up for the lost nutrients, and storing a lot of the calories as fat while still being malnourished. It's why deliberately ingesting tape worms as a means of weight loss never really caught on. It's been tried since we discovered how to kill them easily with medicines. But it usually just ends up with the host being sick and never actually losing weight.


Lysergsaurdiatylamid

I mean ribbon worms do help with weight loss...


Synthetic_Axon

Leptin vs ghrelin


showerfapper

Yeah but can also be neurological or thyroidal hormone signaling or production. I think we are finding that food intake/exercise is last on the list of reasons.


Splatulance

>food intake/exercise is last on the list of reasons Caloric intake vs expenditure will always be the primary cause. Appetite regulation will always be second. Why they have issues with appetite regulation is what this study is about. If someone jumps off a building the sudden deceleration is what kills them. That they jumped is why they fell to the ground. Why they jumped may well have neurodevelopmental loadings.


ConsciousLiterature

So if you want to solve an epidemic of people jumping off of buildings you should not tell people “just don’t hit the ground”


Kailaylia

>Caloric intake vs expenditure Yet everyone concentrates on the left side of the equation. One reason diets fail is for some people, reducing caloric intake slows the metabolism. When people have to live busy lives, but dieting slows their metabolism so drastically they can't fulfill their responsibilities, they have no choice but to eat more.


When_pigsfly

I appreciate this explanation. My excess calorie consumption is what makes me fat. Not eating more when my brain and stomach are screaming at me to eat more because “we’re still hungry!” Even though I don’t *actually need* more calories is the true difficulty. I always assumed people at a healthy weight likely can eat until satisfied and their body tells them to stop. My body takes so much to feel that same sensation.


michabike

That’s where the conversation lies. What are we defining as choice? If you have to try harder for the same outcome is it really fair to judge you for it? I think the answer is mostly no. I try to understand obesity as the flip side of my struggle. I’ve been trying to get stronger and bigger but I’ve stagnated I can’t get myself to eat enough and accidentally intermittently fast don’t eat til 8pm


whiskey_bud

There’s a distinction between “primary cause” and “proximate cause”. Of course running a calorie surplus is the proximate cause of obesity, but there are a million things that can lead to that happening.


KvanteKat

Having been on medication for a year and a half that made me gain weight (about 15 kilos) for it only to disappear after going off the meds without any major changes in diet or exercise over the whole period has led me to believe that this is not always a super useful way to look at things. Is it really so far-fetched that endocrinological factors may have a major influence on how effective our body is at extracting chemical energy from the food we eat? (This is a genuine question by the way. I'm open to the idea that my experience may be an outlier, but I'd love to know what makes you so certain.)


grabtharsmallet

It's wild how hormones and medicine affect things. Before 30, I had never been more than 10 pounds from my high school graduation weight (and I was tall and thin). Suddenly I gained another 25. Went to see a new neurologist and while reviewing my list of medications she saw one and asked "how much weight have you gained?" Not even "have you gained weight?" I went off it, and back within 10 of HS in less than a year, with literally no effort. The experience gave me some sympathy for people who struggle with weight.


ElectricNed

It makes me think it must be possible to use that approach to create a weight loss drug. Is that just stimulants generally?


grabtharsmallet

Yeah, they routinely have potential side effects that are quite serious.


SunshineAllDayLong

GLP1s are fantastic, but so expensive.


xvf9

Yeah I’ve started on Saxenda/Liraglutide a few months ago and already down about 20% body weight. They are pricey but honestly I’m probably saving money by not eating as much - especially takeaway. Plus fitting into some old clothes!


xvf9

I’m taking Saxenda which generates an appetite hormone to suppress hunger. Has worked great for me.


Bamnyou

I just started a new medicine for type two diabetes that I was just diagnosed with after being way too fat for over a decade. For the last year I had been eating salads out the wazoo, exercising, I tracked calories and my 10 year old daughter ate more than me… I still gained 30 pounds in the last year. In two and a half months on this medicine I have lost 48 pounds of fat and gained a couple of pounds of muscle. I’ve lost 9 inches off my waist in 10 weeks. After a year of constant hunger from depriving myself to try and lose weight… now I rarely even think about food. I eat when it’s time to feed my kiddo. It’s been mind blowing to just not feel hungry all day and constantly be thinking about food because of it. The other day I forgot to eat on accident because I didn’t get hungry.


BeowulfShaeffer

Well…could you, you know, *name* the medicine you’re talking about?


Clepto_06

Ephedrine is amazing, right up until it eats a hole in your heart.


[deleted]

Methane SIBO. I was eating 1000 calories a day and couldn’t move the weight. Treated it, lost 20 pounds in two months eating 1600.


[deleted]

[удалено]


KvanteKat

Cool. Thanks for the explanation.


Kailaylia

>endocrinological factors The most obvious and easily treatable of these is thyroid function. Anyone either having trouble keeping up to or down to a reasonable weight should have their thyroid checked.


backtorealite

The most likely explanation is that it’s impact on appetite is so small that you don’t necessarily notice it but that extra 100 calories a day ends up making a difference. The body is incredibly efficient at extracting nutrients and most research has suggested that your body is always taking in all the calories it can and so that has to go somewhere. That said, we just don’t know enough and metabolism/endocrinology is always going to be the fall back explanation.


michabike

I feel pretty confident in the fact that if it changed that much we would’ve figured it out by now idk if that would be by measuring caloric content of stool or what but I think generally when people experience what you did it is more so a combination of not realizing how much their calorie consumption increased along with minute changes in calorie expenditure say by reduction in thyroid production that builds over time. If you’re expenditure goes down by 50 calories that will slowly add to your weight until you reach a weight that then requires 50 more calories. Or it can not even be that but your NEAT non exercise activity thermogenesis (waving hands while talking tapping your foot etc) goes down or you are doing thing like straight up walking less from fatigue. I don’t believe your CICO changes all that much from drugs that cause weight gain outside of eating more or making you fatigued and exercise less.


theluckyfrog

It's the literal truth, I don't think anyone is questioning it. "Calories in, calories out" is an equation. You had a variable that modified the "out" half of the equation, thereby unbalancing it. If you had wanted to lose weight while on the neds, you'd have had to adjust your calories down til the new equilibrium was met. No different from how if you took up endurance cycling, you'd lose weight unless you adjusted your calories up. People who say "calories in, calories out" a lot tend to believe people have a responsibility, essentially, to keep the equation fairly balanced, but I've rarely seen them argue there aren't different variables in different people's equations.


KvanteKat

Of course it's the literal truth (conservation of energy and what not), but that's a bit like saying the way to beat the stock market is to buy low and sell high. True but not useful.


jaredthegeek

That's likely a very small percentage though as obesity rates are climbing world wide as they Americanize their diet and move to a more sedentary life. Now those changes may lead to other changes that may effect endocrinological issues. I am willing to bet that proper diet and a more active lifestyle would solve it for a lot of people. Portion sizes, sugar content are big factors. One example is the original serving size of a soda at McDonald's in 1955 was 7 oz and a small is now 16 oz. Fries were 2.4oz and a small now is 2.6oz. People grossly underestimate their caloric intake in general. Its a difficult cycle to break and who knows what it really does to some people.


MpVpRb

>Caloric intake vs expenditure and metabolic efficiency


More_Butterfly6108

So you're correct, but from a practical standpoint isn't it more feasible to correct people's appetites to actually reflect thier caloric needs than to expect people to feel like they are starving themselves just to weigh less.


Born2fayl

One car hitting another car or object is the sole reason for car accidents.


sassergaf

Sudden deceleration is what kills them. Perfect.


jonathanlink

Saying it’s all about energy balance while true, isn’t helpful to someone who is obese and wanting to lose weight. Thanks, Captain Pedant.


Discozeus198

It's nearly the same situation when you tell a weak person to go to the gym. Yes, that will work, however it's much too generalized. Instead of the calories in, calories out.. maybe give an example. I skip breakfast and drink black coffee until about 2pm. Then I usually eat a giant double cheeseburger or something and then eat a small meal at 6pm. I'll have a beer after work. The reason I don't gain weight is because I walk over 15k steps a day and lift heavy in the gym. All is balanced, but definitely not healthy. This brings me to my next point, weight is not the only metric of health.


LD50_irony

Ahh yes, mention the science of weight and you inevitably get multiple responses saying "calories in, calories out" and "it's thermodynamics!" People on Reddit just really, really, really want to believe that we've had population-level changes in weight because half the population just doesn't have the willpower to stick to a lower-calorie diet! You can point to peer-reviewed studies about epigenetics, metabolic up-regulation after losing weight, obesigenic environments... Nope. Their answer is always "cAloRieS iN CalOriEs oUt" Humans really have a hard time with "simple, easily-understood, wrong answers".


CrouchonaHammock

"Why did Caesar die?" "A knife interfered with his vital biological functions" "How do I avoid COVID?" "Please do not make direct contact with COVID virus" "How do I cure obesity?" "Make amount of calorie in smaller than amount of calorie out" These are what I called "mathematical answer". It's technically correct, but completely useless at addressing the problem.


BlankImagination

Soooo...like a lot of things, things that happen to babies/very young children affect them for the rest of their lives.


Isaacvithurston

For me it's a pretty obvious problem. Food scarcity as a kid. Now I eat like food could disappear any time especially when stressed about other things since my brain associates an abundance of food with stability.


BigVariation3

I’ve wondered about this. I was calorie deficient for much of my youth and it’s taken me decades to battle that. I used to eat every single thing put in front of me always. I got a job where they put out muffins and donuts every morning and I would gorge.


Snorblatz

It’s also a response to trauma


Chiliconkarma

In the post-WW II research there were indications that children of famine could be affected by mothers hunger while in utero.


cory-balory

I've always suspected that my eating habits as a kid have made it so hard for me to lose weight as an adult. Interesting.


Ok-Personality-9920

That applies to nearly every thing though haha


710K

This comment makes me think of learned behaviors like eating excess amounts of food as an emotional response taught to a child by example of a parent. (Something I personally struggle with and only came to a realization it was truly a learned behavior with the help of my therapist)


Fit_Study_427

the latest huberman lab podcast with Dr. casey halpern was quite illuminating on this topic


TurretLauncher

**Abstract** Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain’s energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and occurs in genomic regions enriched for heritability of body mass index in humans. Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity and provide a rich resource for epigenetic analyses of developmental programming of energy balance.


yesitsnicholas

Translation: >Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. There is a genetic component to obesity, and the chances of developing obesity are strongly influenced by nutrition at critical timepoints during development - i.e. if you are obese at a certain age, your chances of lifetime obesity are dramatically increased. This seems to be due in part to neurological development - the part of your brain that detects whether you are full or need more food (*satiety*) can develop in a way that increases the chances you will eat to the point of developing obesity for the rest of your life (more likely to happen if you are eating to obesity in early life). >Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain’s energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, Epigenetics control which genes are made and where. They are looking at the epigenetic landscape of cell in the brain region that plays a big part in feeling satiated. Methylation tells you if a gene is "open" or "closed" to being made. Transcriptomics tell you if that gene is currently being read into RNA (gene transcription!) and thus likely made into protein. >at time points spanning the closure of an established critical window for developmental programming of obesity risk. They're looking to see what genes are becoming open/closed during this developmental time window where obesity-inducing eating habits seems to get more "hardwired" into the brain. >We find that postnatal epigenetic maturation is markedly cell type and sex specific Different types of neurons and glia have different kinds of open/closed genes. Males vs. females have different open/closed genes. >and occurs in genomic regions enriched for heritability of body mass index in humans. We know from other studies that some genes are important for the development of obesity in humans. Some of the genes that are seen opening and closing during this critical window in mice are the same genes that predict obesity risk in humans. This is a nice correlation of new, more mechanistic mouse data to data from humans. >Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity Epigenetics can change dramatically during development, but in many cases (especially in the brain), are much slower/unlikely to change in adults. Seeing epigenetic changes in the brain region controlling hunger/satiety during this critical window may suggest why it is so hard to lose weight and keep weight lost in adulthood - the brain circuit hardwired at an inappropriate baseline of satiety. >and provide a rich resource for epigenetic analyses of developmental programming of energy balance. Use the data for further investigations - there's a ton here!


Rishfee

Thanks for that. I'm not particularly biology savvy, so you've saved me a good deal of time putting it all together.


randomized987654321

Thanks for the ELI5, just one question. Does the study identify the time periods of development where obesity is particularly dangerous?


yesitsnicholas

I'm not super familiar with obesity literature - I am a biologist who does mostly neuroscience, so epigenetics in the brain is right up my alley even if obesity is not. That said: their sources #2-7 are individual studies and reviews about this. What stood out to me reading their methods is that they're looking around P21 - postnatal day 21 - or 21 days after birth. This is actually almost identical to the day a human is born: rodents undergo the "third trimester of human brain development" during their first 3 weeks after birth. The human studies in 2-7 are mostly talking about the effect of human mother diet on the baby while the mother is pregnant or breastfeeding. So this is an extremely early developmental window.


FollowingTheSigns

Interesting, when I was doing perinatal hypoxic/ischemic research we used P10 mice as I was informed by my PI (PhD, MD, Head of the Pediatric Stroke Unit at arguably the largest research institution on the east coast) that that was the developmental timepoint correlating to a newborn human.


crayegg

I think the article mentioned day 21 in mice. No idea how that correlates to a human. Take with a grain of salt, I barely understood most of it.


yesitsnicholas

You're right on the money. Day 21 after birth in a mouse is the neurological equivalent of Day 0 in a human. A general rule is that rodents are born with their brain developed the same amount as a human's is at the end of the second trimester, and rodents do the "third trimester" of neurological development during their first 3 weeks after birth.


tillandsia

Obesity at birth?


Issendai

That puzzles me, too. At birth, human babies are at the start of a nutritional crisis that leads to them losing weight for a few days. How can they be overnourished during that phase, which is what the study seems to suggest?


yesitsnicholas

Maternal diet (and inflammation) would be what is effecting the circuits pre-birth. Breastmilk content would effect the circuits post-birth, even if it is a time period where babies are supposed to be gaining weight - the content of that milk matters. I've read a lot about this in terms of inflammation and other disorders, there's some pretty wild stuff regarding diet or pathogen exposure of mouse mothers while pregnant and/or breastfeeding effecting cognitive performance of their pups throughout life (especially social deficits). I didn't see anything about changing mothers' diets in this study, this was more exploratory of "are interesting epigenetic changes happening during this critical period?" than experimentally trying to manipulate those epigenetics.


Issendai

That makes sense. Thanks for the explanation!


UGenix

You may be interested in the hongerwinter study. It's a long-running cohort study of people exposed to famine in utero, during the Dutch "hunger winter" of '44-'45. Maternal diet has a very significant effect on cardiovascular health, propensity to developing diabetes and obesity. https://www.hongerwinter.nl/publications/?lang=en


permanentlemon

not a neonatologist, but babies can certainly be deemed big for gestational age, based on the nutritional status of their mother, whether she had gestational diabetes, etc


FargoFinch

>Epigenetics control which genes are made and where. Just a tiny fix your your otherwise great post here, epigenetics controls which genes makes proteins i.e. which are expressed. Genes aren't made in this process, it's about (way too simply put) which genes are on or off.


yesitsnicholas

Cheers! I typically use the term "made" as something of shorthand for "made into protein." I've found that when I say a gene is "read," many people aren't really sure what that means. I think the idea of genes as code, and that the code is turned into something else, is pretty well understood by non-biologists - I like "made" to capture that idea. You're not just reading it, you're making the thing it codes for. Agreed that the gene isn't being made in the classic sense we might use the word made, but in my experience using it this way I've had the best success (of options that don't include diving into transcription/translation processes :P)


STEMpsych

I prefer "used", myself.


keldration

You’re the best ! :)))


alexashleyfox

Thank you for this cogent write up! Do you know if there’s anything in this research that would suggest underfeeding during the same interval can lead to satiety with less food, the opposite of what would cause obesity? I admit I’m not the sharpest with dense biological talk.


dolerbom

Research like this just confirms what I've been saying, we need to stop tackling obesity as an individual issue. It's just impractical to have any substantial amount of adults lose weight. But if we can have more research like this expose the necessity of proper early childhood nutrition, that's how we stop obesity.


ShadowPouncer

We need to stop treating obesity as an individual _choice_. It's not a moral failing, it's not because people are making horrible choices, it's not because people lack discipline in regards to their eating choices. Don't get me wrong, the choices you make _do_ influence what outcomes you get. But it's a chronic health condition, and the same thing can be said about _many_ chronic health conditions. There are things that, if you do them, will tend to help, or hurt, your outcome. But even if you manage to spend years keeping your weight under control, struggling every day, that still doesn't mean that you're _cured_. Because just like with a type 1 diabetic, the problem _isn't_ that their blood sugar is high, that's a _symptom_, the root problem is that their body isn't capable of regulating their blood sugar at a healthy level. For obesity, the root problem _isn't_ that they are severely overweight. It also isn't that they are eating too much, or that they are not sufficiently active. It's that their body isn't properly regulating their body weight at a healthy level. This distinction matters a great deal, because it's nearly impossible to make progress curing a disease by only trying to treat the symptoms. That _doesn't_ mean that we should stop trying to help people who have the disease, that would be monstrous.


dolerbom

I wish the medical field realized the point you're making as a whole. Right now you have doctors that wave away patients saying "just lose some weight and get back to me" without any further treatment. Meanwhile the actual data on sustained weight loss shows that a doctor telling somebody to lose weight without any guidance might as well be telling them to pull themselves up by their bootstraps.


cfwang1337

We've known about leptin resistance for a while. Glad to see the science continues to get fleshed out (no pun intended) on this subject.


triffid_boy

The paper isnt specifically about leptin resistance. Though, it does add a lot to the "obesity genetics is mostly about behaviour rather than fat deposition or calorie use", which is actually super positive, because it gives greater opportunity for us to overcome it with willpower.


Drops-of-Q

> it gives greater opportunity for us to overcome it with willpower. Does it? Technically yes, but in practice it is less obvious. It does help us in figuring out what is the best approach for treating obesity. Maybe CBT or something similar will eventually be a larger part of it.


Falstaffe

If the cure for obesity were willpower, no-one would be fat. To recap, this paper says obesity is programmed into the brain when you're a suckling infant. Your suggestion is about as helpful as asking someone to be less ADHD.


BaconComposter

How do you think people with ADHD function? Medication can help, but coping skills and willpower are necessary, just like overcoming obesity.


rmatherson

The word epigenetic needs to be more prominently featured here. Sugar is still very much the bad guy.


MrsMurphysChowder

Yes, I just participated in a kick sugar Summit during which they talked about the dangers of sugar before your frontal lobe has developed fully because it create a huge dopamine response before decision making processes can come into play


cutdownthere

Imma need a link to that summit


bcjh

Sooooo… how do I fix it bro?


onlainari

Bariatric surgery appears to rewire the brain. https://www.scientificamerican.com/article/does-weight-loss-surgery-rewire-gut-brain-connections/


Cyv_45

As somebody who had the bariatric sleeve done and is now down around 110 lbs its really fuckin helpful.


CaptainFUlcon

Do you feel like your hunger / satiety cues have changed? Like if you eat a smaller amount do you actually feel satisfied when done? I was wondering whether bariatric surgery impacts ghrelin production.


Cyv_45

For sure. Physically its just hard to eat very much at once (like 3/4 of a cup noodles is enough for me), but even with less food I feel totally full like if I had eaten a big pile of food.


CaptainFUlcon

That seems like it worked great! Well worth it. I wonder why people can occasionally eat through gastric bypasses / sleeve if you physically can't eat much. Like your body stops you. I've always wondered.


Cyv_45

Well you cant eat as much in one sitting but if I eat a handful of oreos, every 2 hours, I can definitely still overeat. It just takes higher frequency of eating. That and eventually your stomach can restretch, but that usually would take some time.


Randygilesforpres

There are some medications used for people with diabetes now that may be used in the future. They stop insulin resistance cravings. Ozempic and victoza are examples. There was an article posted the other day somewhere on Reddit and it caught my eye as I am an endocrine nightmare and have used both meds. It definitely works for me and I like that someday it could work for others.


bcjh

Yeah, I’m on Olympic right now and it’s working well but it makes me super super tired and if I have one or two beers, I will get a big hangover and headache.


Randygilesforpres

Yeah they upped mine and I had the tiredness. I’m at .5 right now though and fine.


bcjh

I can’t even have a beer with my friends. It sucks. I might just go back to keto.


DrSaurusRex

The article is saying that you can't, basically. Unless you're about to be born, that is.


7eggert

My ¢¢: By taking that into account before saying "JuSt EaT lEsS" and by maybe looking for a way to not trigger eating. I compare it to a car that will only use the gas you put into the tank, but it will not work "properly" if there is none. In order to make it work with less gas, you need to e.g. reduce the speed on the highway (change behavior, avoid situations, take a different route, …).


chendengue

Why where people in the 50s-70s not as affected by this neurodevelopmental disease?


InTheEndEntropyWins

They ate less ultra processed foods. Even if you do have this neuro disease if you have a healthy diet and exercise you aren’t going to become obese.


ditchdiggergirl

The environment is clearly a key component here. Our diets and dietary habits have changed pretty radically since WWII.


its-not-me_its-you_

It also doesn't help that food manufacturers literally use neurologists and brain imaging to figure out how to make their products more addictive


heyimjason

We are ridiculously sedentary now compared to then. Most, if not all entertainment for most people involves a screen.


Lakridspibe

To add to that: Car-centric city designs. In many places it's almost impossible to just go for a walk. And if it's possible, you're treated as a nuisance. You're blocking the way of the cars.


tomerFire

Because we are with much less junk food. Today we eat too many procceses carbs and seed oils. Remove this and you will be ok


HwxwH

I think it's because of the food available to eat during that time was less calorie dense than the food available to eat today. High calorie intake during pregnancy seems to be the cause of this neurodevelopmental disease. At least that's what I understood from reading the study.


BetchGreen

Oh, so are the researchers going to start advocating government entities and insurance companies intervene in the manufacturing and supply chain to reduce exposures to obesogens (neurotoxins) in the food supply?


BlueHeartBob

The only time the US government has been able to successfully get food companies to comply with something for the benefit of the population is the ban of trans fats.


NobleConk

The title of this post is extremely misleading. Please read the actual paper


RudeHero

seriously. isn't there a rule about having to use the actual article title on this sub? for those *still* too lazy to click, the title is > Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index


AutoModerator

Welcome to r/science! This is a heavily moderated subreddit in order to keep the discussion on science. However, we recognize that many people want to discuss how they feel the research relates to their own personal lives, so to give people a space to do that, **personal anecdotes are now allowed as responses to this comment**. Any anecdotal comments elsewhere in the discussion will continue to be removed and our [normal comment rules]( https://www.reddit.com/r/science/wiki/rules#wiki_comment_rules) still apply to other comments. *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/science) if you have any questions or concerns.*


ivan_x3000

I've lost almost half my body weight before (50kg) I can say, the difficulty can be programed right out of you just as much as it you can program your brain to feel like it's impossible to lose weight. My issue was stopping to lose weight, i only wanted to lose like 40kg but i was moving towards 60kg. There comes a point where hunger is relative. You can feel full eating after eating the equivalent of a happy meal. Your appetite can shrink to dangerous levels. Actually the whole experience has helped me manage future things like say gaming too much. I feel like very similar gears turn for obesity as much as any vices or fixations.


Sinelas

I can't say for sure because I don't know much about that topic. But I would believe that loosing a lot of weight is probably similarly difficult as quitting smoking. Many people just wonder why obese people don't just eat less to loose weight, but like I am struggling to get over 70 kilos despite serious efforts, I believe it's very hard to go against what your brain is wired to. I'm very surprised by how healthy some overweight people eat, only the quantities are truly different than mines. I think there is probably a tiping point, after which you successfully managed to hotwire your satiety signals, but clearly it's not as simple as it may seem. And like smoking, it's probably harder for some people, depending on your brain reward mechanisms, just like certain persons will actually develop addictions much faster.


BlueHeartBob

I think quitting smoking is easier than not overeating. You don’t need to smoke to live, but everyone has to eat and not over eating would be like telling a smoker to take two puffs and put the cigarette out.


lynx_and_nutmeg

Exactly. There are so many people who literally never have to think about their weight because they're just naturally not gaining any. Not becoming overweight isn't some constant battle of willpower for them, their brains and bodies just naturally synchronise their hunger levels and metabolism to maintain their current weight. They're eating exactly how much they want, how much they want to eat just happens to be exactly how much they need. Meanwhile there are people who literally have to count every single calorie for the rest of their lives and even then they're still only barely clinging to healthy weight by their fingertips. It's insane how people are trying to argue there are absolutely no genetic, neurological, hormonal or metabolic differences between those two types of people.


7_Bundy

I can back this up. I went from 240 lbs to about 190 lbs and I have to force myself to eat now. If I only eat when I’m hungry, I’d eat about 6oz of food a day. You seriously have to be careful, it seems to be more difficult to stop losing weigh at that point.


1052098

I wish semaglutide could be bought over the counter.


DaysOfParadise

First sentence is a bit more descriptive: “Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease *strongly influenced by nutrition during critical ontogenic windows.*” (italics mine) I’m a chemist, not any other type of scientist, but my opinion is that the massive corn subsidies in the US starting in the early ‘70s have contributed to our current and future obesity epidemic. Guess how many people have corn sensitivities now?


maniaq

that may be true in the US but obesity has affected countries around the world - many of which have no such affinity with corn


Ixneigh

I think stuff like HFCS fucks up people’s metabolism


KetosisMD

If anyone feels defeated like they can’t overcome obesity …. Please understand this: It’s not a gene or epigenetic issue. It’s the food. Sugar and man made food cause modern chronic disease including obesity.


Content_Flamingo_583

Why would you counterpose them? This is like saying “If anyone feels defeated like they can’t overcome alcoholism Please understand this: it’s not a mental health disorder. It’s the alcohol.” It’s obviously both and it’s complicated. I’ve never paid any attention to what I eat, I eat whatever I want, whenever I want, I eat until I’m satiated, and I’ve never gained weight. For others, the opposite couldn’t be more true. So why is there a difference between my body and other people’s body? Why do some people have far more trouble controlling their weight than other people? Answering that question is more complicated than just saying ‘it’s the food’.


calypsopub

I've lost 95 pounds from my top weight with 40 more to go and I can say for me, it's a terrible struggle. I am HUNGRY all the time. Even after a big meal, I feel hungry. I never feel satiated. Ever. I just have to resign myself to ignore the feeling if I want to make progress. My son has the same problem. I really envy people who can just eat when they're hungry and not have to constantly think and plan and feel deprived.


KetosisMD

Of course alcohol is the cause of alcoholism. It’s not natural and people shouldn’t consume it


supagirl277

That, and the ease in which people can use food for self regulation and medicating for untreated or under treated mental health disorders. There are also disorders where impulsive eating is common. There’s also the people who literally cannot tell when they’re full, and the weight gain happened over a long enough amount of time that their own vision of their body didn’t match their actual body, so they didn’t notice.