Tuesday, May 7, 2013

The Neurobiology of the Obesity Epidemic

I recently read an interesting review paper by Dr. Edmund T. Rolls titled "Taste, olfactory and food texture reward processing in the brain and the control of appetite" that I'll discuss in this post (1).  Dr. Rolls is a prolific neuroscience researcher at Oxford who focuses on "the brain mechanisms of perception, memory, emotion and feeding, and thus of perceptual, memory, emotional and appetite disorders."  His website is here.

The first half of the paper is technical and discusses some of Dr. Rolls' findings on how specific brain areas process sensory and reward information, and how individual neurons can integrate multiple sensory signals during this process.  I recommend reading it if you have the background and interest, but I'm not going to cover it here.  The second half of the paper is an attempt to explain the obesity epidemic based on what he knows about the brain and other aspects of human biology.

Dr. Rolls kicks it off with a brief discussion of genetics, just enough to conclude that it can't be responsible for the current obesity epidemic.  I've edited the references out to streamline the text.
These are of some importance, with some of the variance in weight and [resting metabolic rate] in a population of human subjects attributable to inheritance. However, the ‘obesity epidemic’ that has occurred since 1990 cannot be attributed to genetic changes, for which the time scale is far too short, but instead to factors such as the increased palatability, variety and availability of food which are some of the crucial drivers of food intake and the amount of food that is eaten in our changed modern environment and that are described later.
I'll note here that the idea of a gene-environment mismatch is the foundation of the ancestral health concept.  Although it has become fashionable in some academic circles to criticize the ancestral health/Paleo community for "idealizing the past", being unscientific, etc., in reality this fundamental concept is widely accepted and cited in the biomedical literature (as shown above and below).  Few researchers would disagree that a gene-environment mismatch is at the root of the modern obesity epidemic, and therefore that it is valuable to understand where our species came from in our effort to combat obesity. Although some of the critiques of the ancestral health community are legitimate, they often reek of academic snobbery and ingroup identity reinforcement.  The fundamental concept is sound and already widely accepted, so why not cooperate and try to refine it instead of ostentatiously rejecting the community attempting to advance it?

Dr. Rolls then moves on to discuss what has changed about our environment that has increased food intake.  You might find this familiar:
The fundamental concept this leads to about some of the major causes of obesity is that, over the last 30 years, sensory stimulation produced by the taste, smell, texture and appearance of food, as well as its availability, have increased dramatically, yet the satiety signals produced by stomach distension, satiety hormones, etc. have remained essentially unchanged, so that the effect on the brain's control system for appetite is to lead to a net average increase in the reward value and palatability of food which over rides the satiety signals, and contributes to the tendency to be overstimulated by food and to overeat.
Again referencing the mismatch between our evolutionary context and modern environment, Dr. Rolls discusses the ability of food palatability to increase food intake beyond the body's normal 'stop signal' that would ordinarily constrain food intake when an appropriate number of calories have been eaten:
A factor in obesity (as described in section ‘Brain processing of the sensory properties and pleasantness of food’) is food palatability, which with modern methods of food production can now be greater than would have been the case during the evolution of our feeding control systems. These brain systems evolved so that internal signals from for example gastric distension and glucose utilisation could act to decrease the pleasantness of the sensory sensations produced by feeding sufficiently by the end of a meal to stop further eating. However, the greater palatability of modern food may mean that this balance is altered, so that there is a tendency for the greater palatability of food to be insufficiently decreased by a standard amount of food eaten, so that extra food is eaten in a meal.
He also covers sensory-specific satiety, another factor in food intake.  This phenomenon is the reason why we eat more total food when food variety is high, as explained here.
Sensory-specific satiety is the decrease in the appetite for a particular food as it is eaten in a meal, without a decrease in the appetite for different foods, as shown earlier. It is an important factor influencing how much of each food is eaten in a meal, and its evolutionary significance may be to encourage eating of a range of different foods, and thus obtaining a range of nutrients. As a result of sensory-specific satiety, if a wide variety of foods is available, overeating in a meal can occur. Given that it is now possible to make available a very wide range of food flavours, textures and appearances, and that such foods are readily available, this variety effect may be a factor in promoting excess food intake.
And a word about calorie density:
Although gastric emptying rate is slower for high-energy density foods, this does not fully compensate for the energy density of the food. The implication is that eating energy dense foods (e.g. high-fat foods) may not allow gastric distension to contribute sufficiently to satiety. Because of this, the energy density of foods may be an important factor that influences how much energy is consumed in a meal.
It's worth noting that although fat is a factor in calorie density, it's not the only factor.  High-fat foods can be moderate in calorie density (e.g. avocado), and high-carbohydrate foods can be high in calorie density (e.g. crackers).  That being said, all else being equal, higher-fat foods do tend to have a higher calorie density.

The reasoning Dr. Rolls presents in his paper is why I frequently say that the obesity epidemic is due in large part to increased availability of calorie-dense, highly palatable and rewarding foods.  This statement neatly summarizes some of the main factors that influence food intake: food accessibility, calorie density, food variety, palatability, and reward.

I hope this all sounds familiar to regular WHS readers.  The idea is that the brain integrates a variety of factors, both internal and external, into its (mostly unconscious) decision-making process of whether or not to eat.  Some factors increase the probability of eating, while others decrease it.  Changes in these factors (e.g. changes in the food environment due to technological progress) can alter the probability of eating, alter total food intake, and ultimately alter body fatness.  Here's an image summarizing this process, from the last post in my series "Why Do We Eat? A Neurobiological Perspective" (2):


  1. "The fundamental concept is sound and already widely accepted, so why not cooperate and try to refine it instead of ostentatiously rejecting the community attempting to advance it?"

    Oh-so-quotable. Worth reading for that gem alone.

  2. Thanks, Stephan. I would give more weight to the social restraints. If you go out to eat and everyone else is eating birdlike portions, you probably won't overeat.

    But if everyone else is ordering and consuming gargantuan portions of burgers and fries, you'll probably do the same.

  3. This picture summary is brilliant! Tells everything.

  4. Excellent summary, I'll have to move this one to the top of my reading list. One additional factor that I think may be very important is the role of Pavlovian conditioning in conditioning food preferences and increasing the body weight (or body fat) set point, a la Seth Robert's Shangri La Diet. Even in rodents it's been shown that eating potato chips (high reward value and "ditto food" as Seth calls it) can not only lead to increased consumption of potato chips, but also to increased consumption of regular rat chow. That is, junk foods that are by definition highly rewarding (if not always highly palatable) increase appetite in the future. If this leads to increased seeking and consumption of more junk food, a vicious cycle ensues.

  5. My only beef (pun intended) with these studies, papers, what have you, is when they discuss "fatty foods" without defining what a fatty food is, or give an example.

    Is a fatty food an avocado, as you mention, or a do-nut. Is it pure butter from grass fed cows or industrial seed oils. Can you really over consume fat without carbohydrates (wheat and sugar).

    Can you really consume more calories eating nothing but butter or cereal and skim milk. I don't know, but I would bet it's the cereal and milk.

    When they say fatty foods are bad, people immediately think I'll skip the butter and eat that fat-free whole wheat chocolate raisin scone.


  6. I agree with Chuck. Too many studies are broadcast with heads saying fatty foods do this or that, and it's not clear if they mean fat added to standard chow or a low-carb, high-fat diet. You usually can't tell from the Abstract, and sometimes it's not even clear in the article, if you can get access to that without mortgaging your farm.

  7. As Dr. Guyenet discussed in his TED Talk, I wonder if increases in snacking has been the primary driver of obesity? If so, maybe a relatively easy and effective public health campaign would be to tell people "no snacking." It sounds stupidly simple but maybe such a campaign would work?

    Most healthy cultures seem to only eat 2-3 discrete meals per day with no snacking.

    Data on French eating habits:

    "A recent survey conducted by the French government's Committee for Health Education (CFES) found that eating is still very closely linked to a national heritage of consuming good food for pleasure. In France, 76 per cent eat meals they have prepared at home; the favourite place to eat both lunch and dinner is in the home, with 75 per cent eating at the family table."


    Also, eating at weird points in our circadian rhythm, such as with the midnight snack, may affect fat oxidation and LDL level (no control with no snack, unfortunately)


  8. Hi Gretchen,

    "High-fat diets" used in research are usually 40-60% fat and 20-40% carbohydrate (compared to 10-20% fat and 60-70% carb in unrefined chow). They are typically "purified" diets made with refined ingredients and vitamin/mineral supplements where the composition can be precisely known. They usually contain some sugar, though not necessarily a lot. The combination of sugar and fat is more fattening than either one alone.

    The HFD we use in the lab is indeed a high-fat, low carb diet, with only 20% of kcals provided as carbohydrate (~7% as sugar). It is extremely fattening in susceptible strains of mice and rats. This set of facts tends to get certain LC diet advocates riled up, but I'm not sure why. It's just a diet we use to induce obesity in rodents so we can study obesity; it doesn't mean whole food low carb diets have the same effect in humans.

  9. Thanks, Stephan. I think what gets some LCers riled up is the popular press interpretations. Much research is done on rodents bred to get fat when they eat fat, but the popular press implies that the same is true of humans.

  10. I remember Ed Rolls. The undergraduates called him Bread Rolls. He was married to Barbara Rolls in those days of course. He left Experimental Psychology recently and started the Oxford Centre for Computational Neuroscience. Now oddly, this is a limited company. What is he selling? I don't mean to imply his work isn't good, as far as I know it's excellent. But clearly the idea that obesity might be caused by brain damage and nutritional deficiencies is very far from his thinking.

  11. Dr. Guyenet,

    Some time ago in a previous post you observed that when this that or the other problem was attributed to intake of saturated fat, often the problem is really caused by deficiency of omega-3 oils. Obesity induced in rodents due to a high fat diet may in part be due to a deficiency of n-3 fatty acids relative to n-6 intake.

    A recent study noted that animal obesity is "classically induced by 60% fat diets containing 8% of energy as LA." The study found that 60% fat diet does not induce obesity in rodents when ALA intake is 1% of energy and LA intake is reduced to 1% of energy. "This indicates that the causal factor for inducing obesity in the 60% fat diet was the high LA composition of 8% of energy, not the high caloric density."

    The study, "Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Iduces obesity", concluded that the induction of obesity in rodents by the high fat, high LA diet was due in part to to LA-induced increased tissue content of arachidonic acid which are the backbone of endocannabinoids which cause increased food intake. The high fat diet contributes to obesity by inhibiting the enzymes that degrade endocannabinoids.

  12. Great article Stephan,

    Have you looked into the research from Brian Wansink or read his book, "Mindless Eating?" It seems like another under-studied aspect of weight loss and obesity that could have huge implications, especially if combined with the research you've covered so well on food reward.

    Regarding the paleo movement, do you think the name might be what largely polarizes people against it? Obviously we're talking semantics, but the term still conjures images of cavemen in loin cloths for many people. In some ways, it seems better to just call it "science" or "scientific progress" rather than labeling it as ancestral or not, though that isn't as clear when explaining the concept.

    Thanks again,

    - Armi

  13. I'm not surprised LCers get riled up about "low carb" diets containing 20% carb. For me, that would entail eating a couple of large baked potatoes per day, which wouldn't generally be considered low carb. Of course that's lower than a typical diet, but I suspect most LCers would think this not sufficiently low to gain the benefits of LC.

  14. A new molecule of interest may be clusterin. "Here we report that central administration of clusterin, also called apolipoprotein J, causes anorexia, weight loss and activation of hypothalamic signal transduction-activated transcript-3 in mice."


  15. The aforementioned study regarding the obesigenic effect of high LA diets provided an interesting analysis of the effects on weight gain of high fat diets compared to high carbohydrate diets.

    Mice fed 1% n-3 ALA and 1% n-6 LA were fed medium fat high carb diet diets (35% fat and 45% carbohydrates) and high fat,low carb diet(60% fat, 20% carbohydrate).

    Mice on the medium fat, high carbohydrate diet, compared to those on the high fat diet,consumed 6% fewer calories but had a 7% higher food efficiency (weight gain per calorie of food) due to increased conversion of carbohydrates to fat (de novo lipogenesis) and as a consequence weighed about 5% more.

    The results indicate that increased calorie intake of a high fat diet is offset by increased lipogenesis of a high carbohydrate diet.

  16. Hi Stephan,

    First let me thank you for the work you do with this blog, it's very helpful to be given an insight into the reasons behind overeating. You're articles are very wide ranging but if I am able to give you one slight criticism it's that you don't seem to cover enough the use of nutritional supplements and/or medication to help lower intake of rewarding foods. I agree with you on your strategy for reducing intake but you don't seem to give enough attention to dealing with the addiction besides saying abstain which is very difficult for most people. For example I used to have 2 cups of tea every morning with 3 teaspoons of sugar in each one, as soon as I woke up getting this sugar and caffeine fix was the first thing on my mind and if I didn't have it I would have a terrible day. Despite many attempts to stop I just couldn't. I started taking 100mg of 5HTP in the evening and with a few days I spontaneously felt like having tea without the sugar, within a week the idea of having sugar in my tea repulsed me. Later on I removed the milk so it was a calorie free drink and then I switched to decaffeinated with the help of tyrosine.

    I have also come across a lot of research suggesting that obese people have lower levels of serotonin, dopamine and norepinephrine which can be corrected using MAO inhibitors like Moclobemide. In rats Moclobemide reduced anxiety and reduced food intake to normal levels. Also interestingly I found that the Curcumin is a natural MAO inhibitor which gives the same results in rats but may be poorly absorbed in humans.

    The dopamine agonist Bromocriptine also lowers bodyfat and it is well known that serotonin agonists do the same.

    Another strategy is the use of Naltrexone to block the opioid reward pathway resulting in a decreased intake of palatable food. Tramadol also causes great weightloss in a lot of people, probably through both the serotonin and opioid activity of the drug. Topiramate is another drug that causes weightloss.

    Whilst I don't believe that long term use of medication is helpful, I thing the use of it to help you get to where you need to be should not be overlooked. I think the use of naltrexone to block the opioid response and the use of reversible MAO inhibitors with precursors like 5HTP and L-Dopa would help reset the brain by raising baseline levels of monoamines back to normal and restoring opioid sensitivity.

    I think a lot of people using this site would benefit from an expert like yourself taking a look at this side of things and giving your opinion.

  17. Jack C added a piece relating to this study: Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity.

    Many thanks Jack for hunting this one down! Am following up on this. The link to the full study is: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458187/pdf/oby201238a.pdf

  18. Tony, In the aforementioned study (PMID 22334255) rodents fed a medium fat diet (35% fat, 45% carbs)including 1% as ALA and 1% as LA were not obese but became obese when dietary LA was increase to 8% of energy resulting in increased tissue AA and AA-derived endocannabinoids which caused a 2% increase in food intake and a 14% increase in food efficiency (weight gain per calorie). Weight increased 12% and the adiposity index increased by 24% almost entirely due to increased food efficiency, or, to put it another way, due to reduced energy expenditure. I have found a couple of interesting studies regarding the decrease in energy expenditure that results from increased endocannabinoids.

    Two studies (PMID 18755884, 2291402) have shown that increased endocannabinoids result in decreased energy expenditure due to decreased circulating thyroxine and triodothyronine which cause hypothyroidism, ectopic storage and hepatic insulin resistance.

    It has been found (PMID 22425701) that hypothyroidism increases risk of non-alcoholic fatty liver disease (NAFLD). The finding is consistent with studies that show that excessive LA intake causes fatty liver disease (PMID 21457226)due to increased AA-derived endocannabinoids.

    It could be said that linoleic acid elevates endocannabinoids and induces obesity, insulin resistance, hypothyroidism and fatty liver.


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