Sunday, April 21, 2019

Appetite and Genetics

Are thin people thin because they have incredible self-control whereas overweight people have very little? Or could their genetics play a large role?

A story in the New York Times suggests the latter. They describe people with a version of a particular gene, MCR4, who are simply almost never hungry. Self-control has little to do with it. Conversely, people with another version of the gene are constantly hungry. In other words, it's appetite that controls how much people eat in an environment in which food is plentiful, and some people are hungrier than others.

Overweight people often think that, but no one believes them and people tell them (or at least believe) they have no self-control.

I've always thought genes play a large role in controlling appetite. A good example is in my book The First Year: Type 2 Diabetes:

"Having diabetes genes may affect the appetite. Alex E. described the time someone brought some scrumptious pastries to work. A thin person walked in, looked at the pastries, and said, "Oh my, those look good. I wish I were hungry so I could try one." Alex was flabbergasted. He was  hungry all the time and thought everyone else was too."

Of course, genes are not the only factors affecting appetite. Hormones such as leptin and ghrelin and fluctuating blood glucose levels can affect hunger, as can habit, for example always eating lunch at a certain time. If you always have lunch at noon, you're likely to get hungry around noon. Other psychological triggers can affect appetite too. And one can change habits. But genes are important.

The researchers note that the MCR4 genes don't affect metabolism but affect appetite. In other words, if a thin person and an obese person eat the same meal, they'll burn about the same number of calories, but the thin person often eats less of the meal.

Researchers have found at least 300 mutations in the MCR4, and it's likely that mutations in different parts of the gene would have slightly different effects. It had been shown previously that mutations in the MCR4 gene increase the risk of obesity, but the recent study was the first time it has been shown that other mutations in the MCR4 make people feel full even when they haven't eaten.

Unfortunately efforts to develop drugs to increase activity of the MCR4 gene to decrease appetite were halted when the drugs were found to decrease appetite but also to increase blood pressure. Other efforts produced other unacceptable side effects. Clearly, tweaking this gene is possible but not easy. But as more is learned about the gene's effects, useful drugs without side effects might be developed.

And it's important to understand that it's unlikely that dealing with just one gene that affects obesity is unlikely to solve the growing problem of obesity. Many genes are involved, as illustrated by this study. 

As the authors note: "Finally, a clear understanding of the genetic predisposition to obesity may help to destigmatize obesity among patients, their health care providers, and the general public."

So how does this all affect you? Well, if you're very overweight and feeling guilty about it, understand that it may not be your fault. It could be your genes.

However, that doesn't mean you shouldn't try to do something about it if the excess weight is contributing to other problems like high blood pressure or type 2 diabetes. The fact that weight loss will be more difficult for you than for some other people doesn't mean it's impossible. Dump the guilt and  get to work.

You can succeed.

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