New Research Suggests That Obesity Is a Neurodevelopmental Disorder

Consciousness Brain Activity

The study found that early-life molecular mechanisms of brain development are likely a significant factor in determining the risk of obesity.

Scientists have recently proposed that obesity is a neurodevelopmental disorder.

Over the last several decades, obesity has rapidly grown to affect more than 2 billion people, making it one of the biggest contributors to poor health globally. Many individuals still have trouble losing weight despite decades of study on diet and exercise regimens. Researchers from Baylor College of Medicine and affiliated institutions now believe they understand why, and they argue that the emphasis should be shifted from treating obesity to preventing it.

The research team reports in the journal Science Advances that early-life molecular processes of brain development are likely a major determinant of obesity risk. Previous large human studies have shown that the genes most strongly associated with obesity are expressed in the developing brain. This most recent study in mice focused on epigenetic development. Epigenetics is a molecular bookmarking system that regulates whether genes are utilized or not in certain cell types.

“Decades of research in humans and animal models have shown that environmental influences during critical periods of development have a major long-term impact on health and disease,” said corresponding author Dr. Robert Waterland, professor of pediatrics-nutrition and a member of the USDA Children’s Nutrition Research Center at Baylor. “Body weight regulation is very sensitive to such ‘developmental programming,’ but exactly how this works remains unknown.”

“In this study, we focused on a brain region called the arcuate nucleus of the hypothalamus, which is a master regulator of food intake, physical activity and metabolism,” said first author Dr. Harry MacKay, who was a postdoctoral associate in the Waterland lab while working on the project. “We discovered that the arcuate nucleus undergoes extensive epigenetic maturation during early postnatal life. This period is also exquisitely sensitive to developmental programming of body weight regulation, suggesting that these effects could be a consequence of dysregulated epigenetic maturation.”

The researchers performed genome-wide analyses of gene expression and DNA methylation, a key epigenetic tag, before and after the postnatal critical window for the developmental programming of body weight closed.

“One of our study’s biggest strengths is that we studied the two major classes of brain cells, neurons, and glia,” MacKays said. “It turns out that epigenetic maturation is very different between these two cell types.”

“Our study is the first to compare this epigenetic development in males and females,” Waterland said. “We were surprised to find extensive sex differences. In fact, in terms of these postnatal epigenetic changes, males and females are more different than they are similar. And, many of the changes occurred earlier in females than in males, indicating that females are precocious in this regard.”

The human connection

The biggest surprise came when the investigators compared their epigenetic data in mice to human data from large genome-wide association studies that screen for genetic variants associated with obesity. The genomic regions targeted for epigenetic maturation in the mouse arcuate nucleus overlapped strongly with human genomic regions associated with body mass index, an index of obesity.

“These associations suggest that obesity risk in humans is determined in part by epigenetic development in the arcuate nucleus,” MacKay said. “Our results provide new evidence that developmental epigenetics is likely involved in both early environmental and genetic influences on obesity risk. Accordingly, prevention efforts targeting these developmental processes could be the key to stopping the worldwide obesity epidemic.”

Reference: “Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index” by Harry MacKay, Chathura J. Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa and Robert A. Waterland, 28 September 2022, Science Advances.
DOI: 10.1126/sciadv.abo3991

11 Comments on "New Research Suggests That Obesity Is a Neurodevelopmental Disorder"

  1. Brain region sizes has more to do with use. We can see this when people learn musical instruments, or take on other challenging skills. Simply seeing a volume difference for some area is far more likely “effect” than “cause”.

    I think the evidence is fairly clear that Adenoviruses 5, 36, & 37 are the main reason there is much more obesity in the World than there was 50 years ago. If you infect animals with these, they become obese. And we know these viruses have spread like wildfire…mostly in the 1980s. Scientists ethically can’t infect people and see what happens, so saying it is the cause definitively can’t easily be done.
    There are other factors: reduction in smoking (though obviously this is a good thing), stress increases, fetal/infant/toddler lead exposure weakening self-control, reduced iodine levels (too many people swindled into buying pink salt from Pakistan rather than iodized salt) increasing levels of blue light exposure at night and when sleeping, high levels of sexual abuse, cellular phone, game console, and PC use reducing physical activity, some reduction in nutrients in the soil, and ironically the reduced consumption of whole milk.

    What it isn’t is high fructose corn syrup. US consumption went way down, even as obesity was rising.

  2. Meaning that its a learned behavior and you can unlearn it.

    Eat less excercise more. Surround yourself with healthy active people and cut out unhealthy, miserable ones.

  3. Obesity is not simple, nor is it a sign of moral failure. It’s just not. There’s a LOT of science on this. See lepton, ghrelin, check out PH, and other causes of “obesity”. Maybe it’s more then one thing.

  4. Another “scientific” article on obesity that simply confuses the reader into concluding “it’s not my fault”. I sit at the dining table with two seriously obese nieces and my nephews daughter. I watched each of them go from thin and trim healthy youth to bulbous teens and now adults. Each have asked me for advise, which started with cutting out all sugar and eating less. I observed their extreme portion size, bad food type & quality plus near constant sweet/large dessert habits were pervasive.. yet they each told me their doctors tell them they’re healthy and should consider losing a few pounds. Imagine that.. doctors afraid to be honest. In each case I suggested setting weight loss goals (5lb mo), weigh on scales every other day in AM and tracking it visually like a thermometer. I’ve observed EACH of them fail within a day or two to heed the simplist of advice.. (overeating, adding sugar, CHOOSING crap food) “I forgot” or “but it tastes good” they say. Conversely.. my good friend with willpower and commitment lost 100lbs in a year after we reconnected and he saw how I only gained 10 lbs since high school.. and asked how. So keep suggesting some convoluted and complex reasons for obesity and ignoring habits and choices. You’ll continue to foster increased rates of obesity. Doctors, please do your job.

  5. Charles G. Shaver | October 22, 2022 at 12:24 pm | Reply

    Statistically and functionally, the global human obesity pandemic began in the US in 1980 with the FDA approval of the expanded use of added toxic ‘cultured-free’ (can cross the blood brain barrier, as opposed to natural ‘protein bound’) monosodium glutamate (MSG). “Decades of research in humans and animal models have shown that environmental influences during critical periods of development have a major long-term impact on health and disease…” and “epigenetic maturation” (or not) are still fatally flawed based on incomplete evidence due to the failure of mainstream medicine to ever recognize and research acquired and/or inherited chronic subclinical psychosomatic non-IgE-mediated, Dr. Coca’s (my), kind of food allergies aggravated (or not) with officially (FDA in the US) approved toxic food additives (namely soy and MSG; others). As to the differences between females and males, estrogen can likely explain those, especially in consideration of it being protective again uric acid, a major component of my still very, very mild kind of allergy reactions. I first wrote the FDA of some of this in 2005 yet mainstream medicine is still so “dark-ages.”

  6. A big part of the obesity epidemic is the increase in the use of psychiatric drugs that cause weight gain and/or mess with blood sugar levels. This includes ghastly practices such as prescribing antipsychotic drugs for ADHD, prescribing dosages higher than approved by the FDA, and prescription drugs where other less profitable treatments would be more effective.

  7. Earlier the Better | October 24, 2022 at 12:30 pm | Reply

    Epigenesis. Recently, They said some of our forefathers’ knowledge in their lives percolates to us too. Biologists of previous centuries just pulled out various living beings from their habitats and classified them because, that was all that they could do then. We have to do 3 types of studies. Hens just sit on eggs to hatch them. So, We don’t expect much from them. But, there are Various Insects & Birds that build beautiful or annoying nests. The poorest Humans build simple huts for themselves.
    We have to learn whether Insects & Birds are learning from their moms about need to build nests when they become moms in their turn.
    1) Separate them when they are eggs and provide what all they need..mud, twigs, branches, Food etc. Can they build when they never saw their mothers’ nests? 2) Take 10 of a species, meddle with different regions of their Brains and study such impact. 3) Take 10 of a species, Meddle minimally with their Chromosomes and see which will make them lose the nesting ability when they grow up !

  8. Deborah Barges | October 24, 2022 at 3:13 pm | Reply

    ECS has it right, it’s more than one thing. Research shows that iron deficiency causes the appetite chemical ghrelin to increase, causing more appetite until it hits a certain point where the appetite is turned off, possibly because the body needs iron to absorb certain foods. This would explain why the highest demographic of people who have anorexia nervosa are young women who have been having a period and therefore losing blood and therefore iron for a while to the point that they’ve depleted stores and the body ends up stealing it from whatever causes ghrelin to increase so drastically that it turns off their appetites. As someone said, not a moral issue. A chemical one.

    Of course, stress depletes nutrients. So a two-pronged attack or multifocal. Probably more factors as well. And certainly if someone thinks that they are overweight and stops eating foods that have iron at that time, that’s another contributor. but it could be that some girls have an anorexia nonervosa as well.

    In studying ghrelin, I stumbled across research showing that pigs will gain weight on the same amount of food when they are given copper. It’s also given for diarrhea, so it may help the food stay in place to be absorbed more, but it also increases appetite because copper can reduce iron in the body. Maybe it merely prioritizes it away for certain uses but it can increase ghrelin and thereby increase appetite as well.

    they feed extra copper to pigs and poultry to get this effect and make them larger for market.

    Then they feed them to us and are surprised that we’re gaining weight.

    They shouldn’t be surprised.

    One of the chemicals that helps the body bind copper correctly is silica but the FDA says we don’t need it so it isn’t in vitamins. They’re increasing copper but not a chemical that helps control it.

    Our bodies expected that silica would be in every glass of water that we drink but in cities it can be completely absent.

    The same is true of calcium and magnesium. They tell us to take calcium in huge doses everyday and that may explain why.

    So if the missing calcium is so important, what about the silica and the magnesium? Some people may have developed in areas where there was lithium in the water, and it is found beneficial for some people against Alzheimer’s. Maybe it’s the people whose bodies became used to with him genetically or epigenetically through mutation or putting bookmarks in the jeans over generations of exposure to lithium, so that for them, I should say us, it’s a necessary nutrient. The carbonate form lasts longer in the body, but the aspartate form and some people use the originate form, highly effective and doesn’t have the side effects of interfering with the ability to walk correctly, anecdotal to you but experience to me, and don’t affect the thyroid as strongly; that’s not anecdotal but science that lithium carbonate effects the thyroid.

    It’s also interesting that of the European union, the major block on the European continent, people are gaining weight at approximately the same rate everywhere.

    But people in France are doing it from a lower weight than everyone else around them. And they don’t have folic acid supplementation in their grain products. unmodified folic acid can build up in the blood, especially in people with an iron deficiency, and people who don’t have enough bound copper and too much free radical copper end up with iron deficiencies. So the low bound Copper from lack of silicon and water accented by the extra copper in certain meat products in some areas, causing an iron deficiency could potentially worsen the overweight problem when people are eating folic acid, and one article suggested once a day was fine but multiple times a day was a problem, so eating folic acid in every grain product during the day.

    There’s other possible causes for that, but these show other directions, even if it isn’t folic acid in France causing people eating fat rich French food to nevertheless be thinner than their neighbors. if this isn’t the mechanism, then something else is.

    So I agree, this is a multifocal problem.

    It would be interesting to compare the weight of people not just to live in areas with hard water but who actually consume hard water, and look at the contents since hard water obtained naturally is different in different areas, and in some cases could be contaminated which could cause a weight gain if it is a heavy metal that is removed from the body using zinc allowing copper to increase, again potentially going free radical or causing iron to go deficient, or both.

    articles have noted that the calcium in water, which could easily correlate with the silica and water depending upon area, also correlates with less high blood pressure. Rats in at least three studies fed silica have lower blood pressure, and also some studies have shown weight loss as well.

    Silica in water has been linked to greater bone density, one study showing that the half of England that has more silica naturally in the water, the other half being depleted from the ground over time, has better bone density. It would be interesting to see if they are also on the average lower in weight and whether their blood pressure is better on the average as well, considering that many will be having filtration that will get rid of the silica and calcium and magnesium.

    Certain well Waters have been linked to less male suicide, which they tried to link to lithium but could not. Since men need 3 mg more zinc per day than women do, it is possible that zinc and well water could be related to male suicide and therefore also male happiness, so zinc could be a benefit for men if it is naturally in water and happiness could increase antioxidants which could make the body able to lower the weight or take care of other health issues.

    If the body is depleted of any nutrient, it might choose to demand more food from the personality in whatever way it can, including cravings, and by not being able to build neurotransmitters, unhappiness which could lead to overeating which could lead to filling in the nutrients and thereby cause a cycle where the unhappiness is improved physically as well as emotionally by overeating, and a physical benefit is something the body is going to enforce.

    And sugar is one of the foods that is higher in silica.


    I’ve heard other claims for other situations that we deal with in cities or in general and I suspect that most of them are correct to some extent.

    The problem is multifocal, and must be addressed multifocally, each individual element separately.

    the research on the Pima Indians showed that if a woman could stay lower in weight during her pregnancy, that her children didn’t have as strong attendance to be overweight throughout their lifetime.

    if all these different mechanisms contribute to the mothers being overweight when they are pregnant, then that’s just one more mechanism that needs to be addressed, but we need to address why the mothers are being more overweight.

    If folic acid supplementation was a major contributor, which has not been ascertained, then it could explain the timing and the rate of increase because it was added to grain products in United States in the late 1990s, so the epigenetic result would be building up since then . . . Possibly at about the same rate as the increase in autism, separate from other causes such as heavy metals in baby food which bind zinc to remove them from the body, zinc being a necessary nutrient for the brain.

    Likewise with folic acid supplementation, if there is not enough iron to process it into the body correctly, the body uses zinc but at a much higher rate then it would you require of iron, causing a zinc deficiency, especially since they tell women to take the synthetic B9 we call folic acid, used because it is more stable with cooking (but doesn’t that mean the body’s going to have to work harder to use it as well?) during pregnancy rather than natural forms like folinic acid, for the potentially too fast acting methylfolate that is the form of the body uses immediately, like cash in hand versus the more checking account form at requirement of folinic acid.

    Not only is it a multifocal concern, but it’s causes will affect other problems and cause other problems. When people are looking back at the Paleo diet and the Paleo lifestyle, they need to look at the contents of the water that our ancestors and their specific ancestors drank and adapted to, and start putting it back in the diet somehow. And avoid things that are synthetic like folic acid, and heavy metals that are dangerous. Just a few items to add to epigenetics as mechanisms we can try to control the overweight problem.

    • Charles G. Shaver | October 25, 2022 at 8:24 am | Reply

      Thanks for a wealth of information, Deborah. You make it even clearer that so-called “modern medicine” is so ‘dark-ages,’ with so much emphasis and research being on drugs and genetics and so little on food quality and nutrition. Yet, there are factors you don’t seem to be aware of yet which I know to be highly relevant (e.g. me, above). I have more on the ‘About’ page of my Odysee dot com/@charlesgshaver video channel. Be well.

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