Do you love to eat? Or do you not love your food enough?

OMG, teh blags aspoloded! And it’s all revolving around Dr. Isis. I urge everyone to check out Bora’s post, it generated some great discussion and it appears that people are friendly again. And Bora said nice things about me, which I always urge people to read. 🙂
It’s that time again! What time is it? It’s time for Sci to give Journal Club. I know, it just happened. But I’m a relatively senior grad student, and our Journal Club is very small, so it happens fairly often. And so, I need your help. Luckily, this time I have narrowed the field to two possibilities, which is especially good as I have about three days to put it together. In fact, both of these papers I got from posts by other lovely ScienceBloggers, though unfortunately I do not recall which ones. I owe you hat tips!
So which one? Which one? Here I present to you the first option: Stice et al. “Relation between obesity and blunted striatal response to feed is moderated by Taq1A A1 Allele” Science, 2008.

I love food. I often say I became a distance runner purely so I could eat everything I want, when I want. I could do entire memes about food…well ok, certain foods. Brussels sprouts will forever remain anathema. But I could write beautiful poetry on the subject of avacados. And pepperoni pizza. And steak. And chocolate. And caramel and pasta and pesto and garlic-stuffed olives and popcorn and pears and beer and Thai and sushi and honey and marshmallows and trsicuits and cheese and more cheese and bagels and bacon and blueberries and blackberries and peanut butter and toast and grapefruit and key lime pie and salmon and homemade mac and cheese… and you get the idea.
The vast majority of us enjoy food, or at least some foods. Obviously there’s a very good evolutionary reason why. If you didn’t enjoy eating, you wouldn’t do it, and your body would have a pretty tough time holding itself together. Food seeking is one of our primary drives, along with sex and a healthy sense of self-preservation.
So is food addictive? More specifically, do people who compulsively overeat have similar brain changes to people who are addicted to other substances, such as cocaine? And are there genetic factors that could influence compulsive overeating?
To address these questions, the authors of this study looked at groups of young women, both lean (BMI under 25) and obese (BMI over 30) (unfortunately, they weren’t very clear in the methods where they placed the cutoffs). They put both groups into an MRI scanner, and then pumped either a chocolate milkshake or water into their mouths. When the patients tasted the liquid, the scientists looked for activation in an area of the brain called the dorsal striatum, containing an area called the caudate. This area of the brain is high in dopamine receptors, and is know to play a role in something scientists like to call “consummatory food reward”. In real people terms, this means when you eat a happy food, the caudate lights up. We know that the caudate responds to the ingestion of chocolate in people of normal weight, and we also know that too much food will result in this area of the brain becoming desensitized.
What they found was that patients who were obese had caudates that reacted LESS to the chocolate than lean patients. The obese patients did not respond as much to the chocolate milkshake, even though they kept sipping at it.
So why is this cool? Well, other studies have found that obese patients have lower levels of the dopamine D2 receptor in the caudate than lean patients. Low levels of D2 receptors results in lower responses to natural rewards such as food. So this means that people with low levels of D2 receptors could be overeating because food just isn’t as “good” to them. It tastes the same (they recorded similar levels of how pleasant a chocolate shake was), but it just doesn’t cut it in the brain, possibly prompting patients to continue eating to make up for the food reward they are missing.
So do these patients have lower levels of D2 receptors because they are addicted to food? Is this caused simply by overeating for long periods of time? It’s possible that there are genetic factors. We know that there are plenty of genetic factors involved in obesity, from leptin malfunctions to even where your body decides to store the fat you have. The authors of this study were looking at one gene in particular, known as TAQ1A. This gene fragment is linked to levels of D2 receptors in the brain. And of course this gene has various alleles, known as A1 and A2. It turns out that A1 is dominant, and that people with A1 allele are more likely to be obese than those with A2. AND, though all obese patients showed a reduced response to a sweet solution, people with A1 have reduced numbers of D2 receptors, and their response to a sweet solution was even lower their their obese counterparts without the Al allele.
Finally, the authors took a bunch of adolescent girls, ran them through the rame tests, and then tracked them over a year to see how their BMIs turned out. They found that girls with reduced caudate responses in the girls predicted an increase in BMI, and that this response was even larger in girls with the A1 allele, implying that te A1 alele contributes to the development of future obesity, possibly through changes in D2 receptor responses to food in the brain.
One of the things I found incredibly cool about this study is how similar the changes in D2 receptors are between obesity and substance addiction, particularly cocaine (as that is the literature that I know best). The authors mention that the dorsal and ventral striatum may play different roles in encoding food reward. The ventral striatum (containing my favorite area of teh brain, the nucleus accumbens), may encode the receipt of food reward (“awesome! Reese’s!”), while the dorsal striatum (containing the caudate), may encode the actual comsumption and processing of the reward (“mmmmmm, peanut butter, so delicious”). This parallels very nicely with a lot of literature I’ve seen on how cocaine addiction forms, with the ventral striatum responding to the receipt of the drug. Over time, the reward processing appears to shift from the ventral to the dorsal striatum, which appears to be at least partially responsible for the craving associated with addiction.
Not only that, but the specific receptor changes are also amazingly similar. Cocaine addicts are known to have reduced D2 receptor levels in the dorsal (and ventral) striatum. This is because cocaine itself increases dopamine levels in the brain, and when receptors are hammered with high levels of dopamine, they tend to desensitize. Dopamine levels aren’t just high when you’re doing crack, they’re also high when you eat tasty foods, and so people who are overexposed to tasty foods might desensitize recpetors that way, though there is probably the genetic component involved.
While I think this study is excellent and answers many important questions, as well as opening up new directions for control of compulsive eating, I feel that there is a chicken and egg debate still remaining (and the authors, as they say in their discussion, entirely agree with me). Do the obese patients have lower D2 levels in the striatum because they compulsively overeat? Or do they compulsively overeat because they have lower D2 levels in the striatum? While the differences scene in the TAQ1A gene are interesting and imply that some initial differences may be innate, environmental factors may still play a very strong role.
I think you could answer this question with a longitudinal study (a study over a long period of time), tracking genotyped children, their eating habits, their D2 levels, and their BMIs. Of course, it’d be very hard to do this in human children, but I think it might be able to be done in monkeys, or even rats, depending on whether or not monkeys or rats have the two versions of the TAQ1A allele, or something analogous in those models. If you could look at D2 levels early in life and find innate differences, it would be compelling evidence that genetics plays a large role. Coversely, if you found no differences in infancy and larger differences in D2 only after weight differences had already manifested, it would imply that behavioral and environmental factors played a role in overeating and the resulting change in D2. Of course both factors are at work, but a longitudinal sudy might allow you to separate out how much of each is involved. This would be a long and difficult study, but it might yield valuable results. For all I know, maybe they’ve already started! Of course, if you could do this is humans, the results would be even more applicable.
And this study makes me wonder. I did a quick search for TAQ1A and cocaine addiction, and found one study linking it. Could the genetic correlates underlying cocaine addiction and overeating be similar, beginning from changes in D2 levels? And if this IS the case, what leads some people to over eat, and some to snort cocaine? Is it merely an opportunity thing, or are there further environmental and genetic changes that make one or the other more likely (as I’m sure there are)?
So this is option number one! Option number two will appear…as soon as I get around to it.
E. Stice, S. Spoor, C. Bohon, D. M. Small (2008). Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele Science, 322 (5900), 449-452 DOI: 10.1126/science.1161550

6 Responses

  1. The non-sciency casual reader says: cool post. And in my non-sciency way I have to ask – is that area of the brain responsive to the actual chemicals in the food you’re eating, or is it more psychological?
    Also, I have an awesome recipe for brussels sprouts. IT WILL TURN YOU. Mostly because it requires a combination of butter and olive oil and a preparation that more or less drowns out the brussels-sproutiness.

  2. As I am obese, and one of those for whom stomach reduction has not worked, I’m very much interested in answers to all these questions.
    Though I know you’re interested in brain stuff, I also wonder what role the pancreas plays. Having an alcoholic brother who cannot get enough sweets and a Type II diabetic mother makes me wonder if there’s a connection somewhere. And it wouldn’t surprise me if the connection were somewhere in the brain.

  3. Scicurious, I don’t even need to see the other option because I vote this one. Seriously? They used chocolate freakin’ milkshakes. I would have volunteered for this study in a heart beat!

  4. Hi SciCurious,
    I would vote for this study only. Also was wondering if I was the fellow ScienceBlogger from whom you picked this story:-). I had written about it here , though I am sure others in the blogosphere would also have covered it!!

  5. Hi Sandeep! I think you were one of the ones who blogged this study. Hat tip to you!
    Ericka: the brain does respond to the chemicals in the food. High levels of sugar and fat will cause increases in dopamine much more than lower levels (which is why low fat ice cream will NEVER be as good). But I’m sure there is also a psychological component. People have told me that chocolate makes me feel better, that chocolate makes everyone feel better, and that therefore I will feel better when I eat it. Chemicals aside, there could definitely be a social component there.
    Donna: ooooh boy, the pancreas. I actually did a post on diabetes recently, which might help a little if you have questions about type II. But yes, the pancreas does play a role in food processing, as levels of insulin determine how much sugar will get to your brain. But in this case, it’s the signalling of reward from taste and sight that is activating the brain areas. There are also lots of signalling chemicals coming from your gut and fatty tissue (like ghrelin and leptin) that play a role in determining how full you think you are. And of course all of this is kept in homeostasis to keep you at what your body thinks is a good weight. If one of these things is knocked out of whack relative to the others, you can upset the whole system.

  6. I don’t enjoy eating, but I like to be strong and muscular, so I force myself to eat above maintenance to support my weightlifting.
    The determinant of whether I’m going to eat something is whether it’s healthful, flavor is very low in importance although healthy food is often flavorful.
    When I for whatever reason take time away from weightlifting I often lose 50-60 lbs on account that I drastically reduce my calories.
    And to comment on the cocaine bit; I’ve never used cocaine, but I did start smoking at 13, however, I didn’t have the money to support the habit, so I easily quit 10 months later. My friends were unable to quit. I took up drinking and smoking cannabis at 14 and quit at 17. I doubt there’s a drug I couldn’t quit with ease although I’m not interested in testing that hypothesis.

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