Diabetes Forecast

Fat's Attack

By Andrew Curry ,

Nicole Stob, PhD, has bad news for people trying to keep weight off. Fat, it seems, sometimes has a mind of its own.

Last year, the University of Colorado—Denver researcher set out to test whether liposuction was a permanent weight loss solution, with the help of a grant from the American Diabetes Association. Working with the University of Colorado's Robert Eckel, MD, and Teri Hernandez, RN, BSN, Stob recruited 39 healthy subjects who felt they had "problem areas" of fat and offered them reduced-cost liposuction surgeries. (A control group will be monitored for several years and receive reduced-cost surgeries at the end of the study.) The liposuction (conducted by Christopher Law, MD) was usually minor, and cos­metic—the most fat removed from any one patient was about 10 pounds.

Before and after the surgeries, Stob took tissue samples and extensive body measurements. "We wanted to see if the removal of fat would affect insulin sensitivity or weight regain," she says. Since liposuction is traditionally a cosmetic surgery, there are few long-term studies on whether it is a permanent solution to excess weight.

Nicole R. Stob, PhD
Postdoctoral Fellow, University of Colorado– Denver Division of Endocrinology, Metabolism, and Diabetes
ADA Mentor-Based Postdoctoral
Fellowship awarded to Robert Eckel, MD

As Stob and her colleagues monitored the study participants over the course of a year, they saw clear results. "We do see fat coming back after surgery," Stob says. She's still analyzing the results, but initial tests using skin-fold measurements showed that the weight seemed to migrate: Women and men who had fat removed from their hips, thighs, and belly seemed to put weight back on higher up—the shoulder blades, for example. "Even in lean individuals, the body tries to defend that fat mass," Stob says.

Her results support a set of theories that have been circulating among scientists for decades. The "body weight set point" idea, proposed by the University of Wisconsin's Richard Keesey, PhD, suggests that everyone has a preprogrammed weight that is actively regulated by the body's metabolism. Other researchers think that external social and environmental factors have more of an impact on some people than on others, prompting them to eat more. This is known as a "settling point." If these theories are correct, then the brain and body may sometimes actively fight weight-loss strategies like diets by adjusting metabolism or appetite to maintain a certain weight.

For the millions of Americans whose excess weight is a contributing factor for type 2 diabetes, understanding the metabolic processes behind weight gain and loss is key for treating and possibly preventing the onset of type 2. But so far, no one really knows why—or how—the body works so hard to keep its weight the same. Some have pointed to evolution to explain the phenomenon. For hundreds of thousands of years, prehistoric people couldn't rely on a steady supply of calories. If a hunt went well, they might have a serious feast—but it could be followed by a long stretch of famine. People who were able to store fat for the lean times would have an advantage. "Fat mass is a really dense energy source," Stob says. Storing it would help prehistoric people survive between hunts.

Today, though, famine is hardly the issue. "We're on the flip side now," Stob says. "We live in an era of abundance." Metabolic mechanisms that developed over time to help people survive by storing fat for the future may now be working against them, contributing to obesity—and then to diabetes and cardiovascular disease.

Stob's liposuction experiment is a way to explore the "how" question. After their liposuction surgeries, subjects weren't asked to change their diet or exercise habits. And they had no health problems aside from a little extra fat where they didn't want it. "We recruited very healthy individuals—not overweight or obese, but people with problem areas," Stob says.

Using the samples she collected before and after the surgeries, Stob is focusing on what happens at the cellular and genetic level when fat is removed. By comparing genes that are active before and after surgery, she hopes to isolate some of the genes that switch on when fat disappears and tell the body to put it back. One early clue: Genes that prompt the production of collagen, part of the scarring and healing process at the site of liposuction, are more active after surgery. "There are definitely signals that are turned on," Stob says. "Maybe the body wants to restore the removed the fat mass, but it can't locally because of scarring—so it puts it back elsewhere."

Besides providing a fresh look at the aftereffects of liposuction, Stob's study is potentially a step toward isolating the genes responsible for short-circuiting the struggle to keep weight at bay. "People want to lose weight, but it's so hard to keep it off," Stob says. "Even if you're sucking it out, the body tries to put it back."



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