Sunday, July 3, 2011

Diet-Induced Obesity and Brain Changes

At the beginning of this year, an interesting French study was published, Changes in Brain Activity After a Diet-Induced Obesity.  Don't get too excited - they used pigs, not humans, specifically "mini-pigs," which sound awesome.  In short, they put two sets of pigs on either standard pig crap lab diet with controlled calories to keep them lean, or a crap lab diet with extra carb and extra fat ad libitum for 5 months.  They did SPECT scans of the pigs' brains before and after, and also (in a separate paper) were able to determined that the now-obese pigs had insulin resistance.

First, though, let's start with some human data and take a tour of some parts of the brain.  Let's introduce ourselves to the prefrontal cortex.  Okay, so when Tom Naughton does his head bangs on his desk, I'm guessing he's whacking his prefrontal cortex (which we are going to call the PFC).  It's the area that hangs out over your eyes.  Fortunately this habit has not seemed to harm his brain function, if his recent terrific articles are any measure.

Now the prefrontal cortex is more developed and extensive in humans than any other primate,  and it is responsible for what is called "executive function."  That is, the PFC helps us predict outcomes, prioritize, modulate our emotions to socially acceptable norms, and helps us sort out the best options given conflicting data (reasoning, basically).  It is a bit like a policeman for your brain - sure, it would be super fun to get drunk as a skunk and throw beer bottles off your roof at the neighbors  - but your policeman says, er, no, that might get you in trouble.  Drinking alcohol, in fact, disinhibits the PFC which enables you to ask out the girl you wouldn't have approached sober.  Of course, if you are making a selection with impaired reasoning, the girl you ask out might not look quite so good to you sober…

But back to obesity.  Our brains do play a major role in whether we gain fat or not.  And part of what happens in obese humans is that the prefrontal cortex seems to be less active than in lean humans.  This finding is especially interesting in obesity, as the PFC sends nerve fibers to the core appetite regulation part of the brain (the "central orexigenic network") - presumably, when fully active, the policeman is shaking his night stick at you when you want to go to the fridge for that second helping of ice cream.  Nuh uh.  You have had enough. If the policeman is offline, it may be easier to consume extra helpings.  (I'm not sure I like the policeman analogy so much - too close to lack of willpower or gluttony and sloth, but it does fit into the model of weird modern food poisoning our brains, so that the reasoning piece of our appetite regulation machinery is shot.)

Now the question is, obviously - do obese humans start out with underactive PFCs, or is it acquired along with obesity? Well, women who were obese with underactive PFCs  regained their frontal lobe function with successful weight loss.*  This evidence would suggest that underactive PFCs aren't hard-wired, but depend upon the environment, including nutrition.  However, a study going the opposite direction - starting with lean humans and making some obese with controlled overfeeding for an extended period is a tough sell to the institutional review board these days.  So it is easier to use mini-pigs, who also seem to have particularly well-developed PFCs.

Let's look at the experiment.  17 pigs, 9 kept lean and 8 made obese.  One of the SPECT scans in one of the obese pigs was "unusable" so the data is for 9 lean and 7 obese.

The standard diet was composed of 33% barley, 25% wheat bran, 12% soy shell, 10% wheat, 10% sunflower meal, 6% soy meal, and other minor components.  Fat provided 2.17% of the total nutritional value.
Well, if in much of pig evolutionary history they were set loose in a warehouse of a cardiologist's favorite Power Bar ingredients, perhaps this is what the minipigs would eat these days and stay nice and lean and metabolic syndrome free.  In this experiment the pigs were fed 102 calories per kilogram each morning, and the pigs dutifully ate their swill in one meal and did their piggy things and stayed lean.  Since calories are calories…though I will get back to the standard diet later...

Now the obese diet:

…eight animals were fed with a Western Diet (WD) enriched with carbohydrates and lipids offered ad libitum during 5 months (one ration offered at 0900 hours and calculated to exceed daily calorie consumption of the animals.  The WD was composed of 32.65% wheat, 15% soy meal, 12% wheat bran, 10% barley, 10% sunflower oil, 10% cornstarch, 5% saccharose, and other minor components.  Fat provided 22.74% of the total nutritional value.
Gak!  Enough said.  I wonder if this was that high-oleic sunflower oil.  Anyway….

The results of the experiment - well, one interesting thing is that the dietary pattern of the fattening pigs changed.  The control pigs ate all their food at once, each morning, but as the "Western Diet" pigs became more obese they would eat 4-5 meals a day, and then spontaneously fast for a day or several days.  By the end of the 5 months, the lean pigs weighed 38 kg on average (which is about where they started).  The obese pigs weighed 67.1 kg.  That's pretty impressive for five months.  The day before the final brain imaging, the lean pigs ate 1561 calories each, and the obese pigs ate 2183 calories each.

And, as expected, the brains of the obese pigs did indeed have decreased activity in the PFC, both in the dorsolateral prefrontal areas and the anterior prefrontal cortex.  In addition, there was a lessening of activity in some brain areas associated with the "reward system" (specifically the nucleus accumbens, the ventral tegmentum, and the nucleus pontis), which is consistent with the addiction literature - people who are addicted to something have less activation of the reward areas of the brain in response to the addictive stimulus than people who are not addicted.  Thus addicted people need more and more of the stimulus to feel reward.

A key finding is that the decreased activation of the PFC correlated significantly with the final weight of the pigs - so the more obese they became, the more depressed their PFC function tended to be.

So, we have learned that in mini-pigs, sunflower oil, wheat bran, cornstarch, and sacchralose is a quick recipe for obesity, and that pigs on a similar diet minus so much cornstarch and oil will stay the same weight as long as you feed them controlled calories… (which is something of a weakness of the study if they were trying to prove that sunflower oil and starch make you fat, which they weren't, but it would have been interesting to see what happened if both groups were fed ad libitum. )

So, in all likelihood, given the corresponding human data in the reverse trial and observationally, the PFC does indeed play an important role in feeding signals and hunger/satiety states.  And I'll quote the researchers here:  "Whether the alteration of the brain dopamine system and prefrontal cortex metabolism is a cause or a consequence of obesity is still unknown.  The answer brought by our study is that less activation of the prefrontal cortex is definitely an acquired anomaly related to obesity, and not a "hard-wired" feature."

*I framed that sentence the way the mini-pig paper did, using "regained frontal lobe function" - however,  in the original paper the womens' frontal lobe function was not measured prior to the weight loss, so it is also possible that the women who successfully lost weight were a subset who had better frontal lobe function - but in that study the obese women had decreased PFC metabolism, the lean and formerly-obese women had PFC metabolism indistinguishable from each other.

Also - for more dopamine/frontal lobe/obesity discussion - a post from last year, ADHD and Obesity.

10 comments:

  1. There are so many possibilities here!! I wonder what future PFC/obesity studies will yield.

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  2. The hypocretin neurons I wrote about in the hypothalamus are the main switch that activates or turns off the PFC. This is precisely why the outflow tracts mention by Stephen G do not fit the bill as the dominant cause of obesity. We are merely observing the effect of the central switch. I spoke about that switch in this post and included my references. I am not sure you saw this Dr. Deans. www.jackkruse.com/why-sleep-and-leptin-are-yoked/

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  3. This seems consistent with the fact that most of the appetite dysregulation/overeating/binge eating behaviour seems almost exclusive to Standard Western Diet. Anecdotally, appetite and "self-control" also seems to re-set in the context of primal/paleo/traditional diet, personal experience confirming this. 
    I guess now we have to be careful that obese patients caught with a hand in a cookie jar (literally) don't say: "My prefrontal cortex made me do it" :)
    Thanks, Anastasia

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  4. I hadn't seen that one yet, Dr. K - and yes, I agree with you that the PFC is likely not primary, but part of the poisoned pathway. The paper mentions some leptin links also but more with the reward pathway.

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  5. Anastasia - I find one of the most interesting parts of the study is that the control diet was crap too - however if you restrict the calories it seems to keep the PFC activated. Not to mention way less O6 and way less sugar...

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  6. Spectacular, I love how well you explain things :).

    It would seem that the best strategy for sticking to a particular diet would be to rid the house of all bad foods and never venture into the center of the supermarket so as to avoid situations where bad food is available and the PFC has acompromised ability to check its subconscious exhortations. Although many will probably have trouble doing that, people like to think that the PFC is all that influences behavior, and then they disregard all the instances that a cookie or handful of potato chips enters their mouths, but accepting the problem is the first step to the solution. And understanding why there is a problem and its nature tends to help.

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  7. Very interesting. From my own experience I can say that when I eat icecream or candy, which are the most powerful binge eating triggers for me, I'm fine if I limit myself to one serving (although I will crave more). However if I let myself have more than one serving my otherwise reasonable relationship with food goes out the window and I will start to binge until I feel disgusted. There is no stopping it and I totally loose control.
    I have always been confused by this because I'm a very controlled person in general and logic and reason are my primary personal traits but it's like a switch goes off and it usually takes me a day or two to get my reasoning back.
    It would be interesting to measure PFC metabolism during this period and see how dopamine levels change.

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  8. I think Mark S intuitively recognises this aspect when he talks of Primalising your Pantry before you begin Primal.

    I have nothing in the house that isn't EF/Primal that way if I overeat (which I do sometimes) the only foods available are good ones!

    Again I note another link to dopamine pathways ... very interesting study.

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  9. If obese people do not have normal sensitivity of dopamine in the brain, and the reward centers of their brains do not function properly during a PET scan, this does not suggest food addiction anymore than a person on haldol is addicted to haldol.

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  10. So I'm wondering how the genetic variants (let's say COMT or MAO) that are related to dopamine regulation play into the (very complex) equation.

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