Saturday, August 13, 2011

Neuroregulation of Appetite

The cause of obesity has been a hot topic in the paleoblogosphere lately.  Let me be the first to tell you that I am no obesity researcher or expert (there, first point goes to Itsthewooo).  All I know is that a few percentage of folks have been obese for thousands of years.  And back in the late 1870s, here's a picture of my great great great (etc.) grandfather's funeral - you might have to click on it to enlarge and squint a bit, but I really don't see any obese people there.

Fast forward to 1919 - here's my grandmother, her mother, and her mother.  Babies were chubby-cheeked as was my great great grandmother.  They lived in the same area and were of the same socioeconomic class as many of the people in the first photograph.

And now 1943.  My father is the baby in this next picture.  As you can see, the children and young or middle-aged adults (including the middle-aged women who have had children) are lean, whereas the older folks have some extra adipose, especially around the middle (again, same area of the country):

And then 1987 - this picture is a tour of the USS Constitution in Charlestown, MA.  As you can see, middle aged folks and even the kids are starting to be chubby, especially around the middle:

These pictures don't tell us much about what we don't already know.  Obesity is a 20th and 21st century disease, that came upon us younger and younger as the decades rolled along, accelerating since 1980 or so.

What caused it?   Video games?  Captain Crunch commercials?  Environmental toxins?  I don't know, but my money is still on the food.  Somewhere between the diets of the Kitavans and the Sioux and most of the people in the world before 1900 and our current diets is the cause of obesity.  

Dr. Pendergrass of the University of Kansas had a great poster presentation up at AHS about the neuroregulation of appetite.  He painstakingly cobbled together a fantastic diagram that detailed the communications between different organ systems, adipose tissue, and the brain.  He highly recommended this paper if you are interested: Stress, eating, and the reward system.

Dr. Pendergrass' diagram was highly technical, inclusive, and awesome, though he warned me that he left out "about 120 known hormonal signals" between the GI tract and the brain.  His also had a great deal of detail regarding the brain and different areas of it, along with specific hormonal and molecular signals and feedback there.  Here is my layperson's version, which leaves out all the crushing detail.  I can't promise all the arrows are leading the right direction (a graphic designer I am not):

It's complicated.  Yeah, leptin, insulin, amylin, CCK, glucose, fat, etc. are all involved.  Yes, once you have metabolic syndrome, dropping the carbohydrate will likely help (how low for how long?  Beats me.)  If you have advanced types of certain kinds of neurologic disease, there's evidence a ketogenic diet can be helpful.  Make sure your micronutrient status is tip top and eliminate food toxins.  Real, evolutionary medicine-inspired food is the easiest way to do that sort of thing.

But anyone who says he or she completely understands obesity is probably lying.


  1. "But anyone who says he or she completely understands obesity is probably lying."
    You don't think they could merely be mistaken?

  2. If they have basic knowledge of physiology, they are not mistaken.

  3. Keep the company of those who seek the truth — run from those who have found it.

  4. Looks like a neat paper. Although I always have to ask how much of cortisol secretion is caused by psychological stress itself and how much is caused by the inability to regulate the stress response due to nutrient deficiencies. Or the inflammatory cascade, or insulin resistance, etc. Seems to be that the deficient, inflammatory and dysfunctional state of the body on bad diets gets the ball rolling for everything else and nutritional changes attenuate everything else, as you have shown before.

    Although once the ball is rolling people should take every hand they can to stop it. Every monomaniacal author is partially right. But yes, lying. What if Taubes had done a pubmed search for "insulin resistance nutrition" or "insulin resistance inflammation", would it still be "the carbohydrate hypothesis?"

  5. It's impossible to "completely understand obesity" any more than it is possible to "competely understand coughing".

    Obesity means nothing more than an excessive accumulation of body fat. This is not a disease. This is a symptom. There are many, many different defects / vulnerabilities which will cause obesity.

    I think it is safe to say the overwhelming majority of modern obesity, which you so illustratively demonstrate above, is not due to novel mutations in the MCR receptor or a mutation in leptin receptors... but rather, it is plain and simple observable effects of very high insulin levels due to a diet which is very good at making high insulin levels.

    In this sense, yes, we understand obesity. It's caused by poor glucose tolerance, which leads to insulin, which leads to body fat, which leads to hunger, which leads to more food, which leads to more insulin, etc.

    All of the above cycle is caused by captain crunch. Obesity surged when modern food loaded with carbs entered the scene. People started porking up around the 70s. This correlates perfectly with women entering the workforce and HFCS being invented. No women to cook dinners + suddenly sugar got a whole lot cheaper = colorful commercials on sunday cartoons about captain crunch, quick meal, etc.

    As can be expected in a free market, as we got fatter and more and more desensitized to sweet tastes (which caused the fattening via loading us up with carbs) portion sizes ballooned. He's offering a 20 ounce soda? WELL I'M OFFERING A 32 OUNCE SODA, HAHA! Buy from ME!

    Destroy a fat person's pancreas and they will not be a fat person anymore. They will also be a dead person, but before then, they will be a person rapidly losing body fat.

    We want obesity to be this big complex mystery because then we can keep selling stomach mutilation surgery and snackwells and diet pills / wellbutrin / amphetmine and januvia and so fourth. The carb theory kills a whole lot of people's livelihoods.

    If the carb/insulin thing was wrong... it would be dead, no one would even talk about it anymore. It has been ridiculed and suppressed for decades but it is still around for some reason. For some reason, some people are inexplicably into this thing. You can't say that about other food fads. It almost suggests that it might be RIGHT.

    I don't think anyone would argue that carbs IN GENERAL make people fat. Obviously people have been eating carbs for as long as we were human.

    It's the extreme density of nutrient poor carbohydrate food entering the scene circa 1970, plus prenatal imprinting, and yes I do think environmental toxins and environmental stresses also damaged mitochondria and glucose tolerance. It's everything about modern society, basically.

    However, once you've been ruined by it, the only way to eat is low carb.

    This is the problem. You have people telling glucose intolerant morbidly obese diabetics that a plate of potatoes without salt or fat is just dandy for them. FACT: a morbidly obese diabetic does not metabolize glucose like a normal person. This general truism about 'taters does not apply to fatties who are glucose intolerant and hyperinsulinemic.

  6. I have the experience of spending first 35 years of my life in a fast-food-free society, however, the most available kind of food was the chip carbohydrate kind. It was very common to see a middle-aged overweight women and almost every old male and female had at least some fat accumulation around middle-section, but children were not fat and teenagers mostly noticeably thin. Thankfully, socialism disappeared 15 years ago, but nowadays you cam see obese 12 years old and younger children, teenagers are still slim. There are a lot of commercials now about sugary yogurts , juices and "healthy whole-grain" products, but Captain-Crunch has not arrived yet and nothing contains HFCS. So far junk there contains less sugar.

  7. Dr. Deans,

    You may have seen this story epigenetics before. This would definitely complicate things further.

    But Bygren and other scientists have now amassed historical evidence suggesting that powerful environmental conditions (near death from starvation, for instance) can somehow leave an imprint on the genetic material in eggs and sperm. These genetic imprints can short-circuit evolution and pass along new traits in a single generation.

  8. Once the problem is understood better, including the genetics, epigenetics, psychology, micronutrient deficiencies, toxicities (from food and from elsewhere), etc., someone will make an even more complicated chart, a flowchart, that explains how to determine the cause of a particular case of obesity, and then prescribes effective treatment for each individual. That time appears to be far away. In the meantime, "don't eat processed crap," "don't eat things that you can't stop eating," "don't eat when you aren't hungry," and various diets (regardless of mechanism, known or not, perhaps based on the presence of insulin resistance or lack thereof) will be the solution. Most people are happy just knowing what works, and so trying to explain the complicated and only partially understood etiology just reduces the chances of compliance with what is known to work.
    Of course, there are people like me who really want to know the mechanism behind everything, so please keep up the great posts!

  9. I don't want to discourage anyone - I would recommend low carb paleo or PHD first for people trying weight loss. I did want to highlight the complexity of the issue.

  10. @David Pier
    Good post but I disagree. I think it is imperative we educate people that WHAT you eat, not HOW MUCH OF IT, is important. As someone who is been into this thing for almost a decade, who has been talking to many many obese people for many years, over and over I observe a major cause of failure to maintain a low carb diet is insufficient data. People have trouble sticking to, maintaining, or even TRYING a low carb diet because they just don't understand why they should. Why should they give up awesome food like bread, for no reason? There are lots of diets out there, their doctors reassure them. What fat person wouldn't PREFFER to eat a diet with cake and ice cream and bread in it? Who is going to voluntarily give up most carbohydrates, unless they are like me and totally understand and *get* the reason why?

    Therefore, we need to educate obese people that their obesity is, very likely, related to some defect in metabolizing glucose, and they should follow a low dietary carbohydrate regimen.

    Regardless of where the defect actually is, the low carb diet will circumvent and calm the disordered metabolic state in one fell swoop. Without dietary glucose coming in, the body relies on fat for fuel, which is easier to process for people who are glucose intolerant. Insulin levels plummet, and due to the lack of endocrine stimulus on fat tissue, blood nutrients are even more elevated and appetite drops accordingly. The more fat leaves the fat cell, the more normal insulin levels are, the lower appetite becomes. Body fat normalizes itself. (To a point; when the patient starts to develop leptin complications at a lower body fat then weight loss may stop, and this will probably occur at a higher than desirable body weight due to hyperplasia of adipocytes from chronic hyperinsulinemia).

    Consider this.
    If you have a patient exhibiting signs of schizophrenia, it doesn't matter if the schizophrenia is from a prenatal virus, it doesn't matter if it is a genetic defect in the regulation of neuronal growth, it doesn't matter if the patient was smoking a lot of bud, it doesn't matter if the schizophrenia is heavy metal toxicity, it doesn't matter if the patient carries a gene which makes him supersensitive to stress mediated cortisol increases and resultant brain degeneration. None of that matters. All that matters is risperdal, zyprexa, seroquel, will help him get grounded and with reality again. The medications which block dopamine and serotonin receptors will calm psychotic thought processes. "Schizophrenia", therefore, is treated with antipsychotics.

    "Obesity", therefore, is treated with a low carb diet.

    Sure there are obesities which are caused by atypical non glucose-metabolism related defects and so a low carb diet is not helpful. There are also schizophrenias which are refractive to antipsychotics. This does not, however, negate the importance of trying - recommending - championing - antipsychotic medication for schizophrenic people.

  11. I think there are many folks who get stuck with just the low carb paradigm - and end up with fat to lose and no more carbs to take out - that if we acknowledge the complexity we can start to find other solutions as we can find a myriad of individual problems lurking underneath the bigger umbrella of leptin resistance.

  12. well, i think obesity especially talking about america's obesity problem is from the boat ride over. before we immigrated, we lived in different climates/environment etc. we lived off traditional staple foods of wherever our family migrated from. they weren't fat. their genetics clicked with their environment and their food staples. their hormonal levels were adapted to the seasons where they came form, the changing food with those seasons. life was peachy.

    then we had to 'come to america'. the first or so generations were fine, still living off what they knew. then we started intermingling everyone's cultural diet into the big ol melting pot. our personal genetics are not set up for that. this changed our stress response and confused the body. this changed how the brain delivered messages to the body. this caused inflammation and this caused obesity.

    obviously, certain foods can be pinpointed like extracted fructose, vegetable oil and wheat which are all things no culture was adapted to. but still, taking an eastern European and putting them on a traditional mexican diet- they'll get fat. their eigenetics don't know Mexican food staples, they know eastern European ones. same if you take a Asian and put him on a tropical diet, they'll get fat.

    its not the carbs, the fat or the protein. it is that certain genes are adapted to certain maintenance of vitamins and minerals and micro nutrients and certain hormonal changes which would reflect seasonal foods and when that changed, so did the body. i have a feeling that another 100000 years from now, the big melting pot will be adapted if we don't end up killing off our species int he process.


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