Physician looks at what keeps people slim

Like many scientists studying obesity, Dan Bessesen, MD, spent years overfeeding rats and putting them on diets in an effort to gain insights into what makes humans gain and lose weight.

What fascinated the chief of endocrinology at Denver Health Medical Center and associate professor at the University of Colorado Health Sciences Center in Denver, however, were the rats who always seemed to maintain their figures, no matter what.

Now, he's turned his attention to people who seem to do the same. With National Institutes of Health support to the tune of $1 million over the next five years, he will be studying the metabolism, genetics and psyche of the people who seem to always stay skinny.

Question: What is the $1 million NIH grant actually for?

Answer: We are doing a longitudinal, prospective study on factors that predict weight gain or the prevention of weight gain. We're interested in how people respond to brief periods of overfeeding, particularly people who remained thin over time in our environment. How do they do that, especially if they overeat?

We probably all overeat periodically, and yet some people overeat and never seem to gain weight.

Q: Why look at thin people, since fat people seem to have the problem?

A: In the past, when I studied obesity, the thin rats were just a control group. But what I realized was that regaining energy balance following a period of overfeeding is a very dynamic process. Obesity is the more passive process. An animal or person overfeeding -- if they don't respond to that overfeeding, if nothing changes -- then they just keep gaining weight.

Another reason to study thinness is that there are many, many possible mediators that drug companies are looking at in hopes of controlling body weight. If we understand how thin people do what they do, maybe that will give us insight into the biologically relevant pathways.

Q: Do you have any pet theories you're looking to prove?

A: From our previous studies, it appears that thin people's bodies just seem to sense the positive energy balance more effectively than people who tend to gain weight over time. Within a couple meals of overfeeding, these thin people have a decreased interest in eating and, following a three-day period of overfeeding, they spontaneously reduce their own food intake just like you should do. People who are prone to gaining weight don't seem to do that as well.

My idea is that thin people have some biologic nutrient-sensing mechanism that is more effective than most of us. As a result, they probably have a range of biologic responses that help them get back into energy balance.

Q: Do you hope to bottle this sensor?

A: That would be great if you could do that. I think we're a long ways from doing that.

Q: How easy is it to overfeed thin people?

A: We put them in our general clinical research center after controlling their diet for a number of days. They eat all their meals here. It's three meals a day, and it's the same composition as their regular diet, it's just increased in calories by 40%.

Q: Do they have to clean their plates?

A: Yes, they do. The whole thing.

Q: Is three days of overfeeding dangerous for them?

A: We do have a safety committee to make sure that nobody gets sick, but it is the kind of overfeeding that everybody does all the time.

I don't think there's any danger. The worst thing that happens is that these thin people feel a little bit sick when they overeat, which is interesting, too.

I wonder if this whole taste aversion system is part of this system that gets turned on that makes thin people stop eating. Not only do they not find it pleasurable any more, but they actually find it aversive. Whereas our obesity-prone people -- they don't seem to reach that point. They overfeed some, and they can say, "That's good. I'll have some more of that."

Q: Could they just be more likely to take antacids?

A: It could be, although they don't report some of these aversive symptoms. I think it feels different in their bodies. I don't think they treat through the discomfort. They don't experience the discomfort.

Q: How easy is recruitment for your study since thin people are getting harder to find?

A: We've been fortunate in getting some attention in press, and every time there's a news story we have had people calling us and e-mailing us and sharing their story. A lot of these people really do feel different, and many of them have their own ideas about why it is. But many of them are really baffled with their own biology. They don't know how they do this.