June 05, 2008

Weight Gain May Not Be Based Just on What You Eat

THURSDAY, June 5 (HealthDay News) -- "You are what you eat" is a frustrating truism familiar to the diet-conscious choosing between carrots and carrot cake. But new research suggests that weight control isn't just a matter of what you put in your mouth, but also how the nervous system is genetically predisposed to process fat.

The theory is based on research with worms that suggests that the brain chemical serotonin -- long known for its appetite control properties -- relies on independent but coordinated nerve pathways to drive not only hunger, but also fat metabolism.

"I want to be clear that there is absolutely nothing in our study that says that good nutrition and activity is not important or not good for you," said study lead author Kaveh Ashrafi, an assistant professor in the department of physiology and the Diabetes Center at the University of California, San Francisco. "But that said, I think that it is important to realize that there is a major contributing factor to body weight that is genetic."

The new findings, based on research with so-called C. elegans worms, is published in the June issue of the journal Cell Metabolism.

Ashrafi and his colleagues noted that, while the worms are obviously smaller and simpler organisms than humans, they are molecularly very close, having about 20,000 genes to a human's 25,000 genes. And both humans and worms have genetically evolved to protect and conserve energy depending on food availability, the researchers said.

Because of such similarities, the researchers attempted to partially deconstruct the worm's nervous system by tracking cell receptors that serotonin connects with when prompting feeding in worms. Then they tracked only those pathways that serotonin activates when regulating fat control.

The researchers were surprised to find that serotonin-directed feeding and fat-burning pathways are, in fact, two separate channels, each operating in a complementary but "molecularly disassociated" fashion.

Also, the worms' feeding behavior appeared to be dependent on their nervous system's shifting gauge -- both genetically and environmentally triggered -- as to how much food was available for consumption. When food was scarce, fat reserves piled up as the worms' metabolic rate adjusted to conserve energy and save fat for a rainy day.

Comparisons to humans are obviously limited by appreciable systemic differences. For example, the authors noted that high levels of serotonin appear to lead to fat loss in the worms, as is the case with humans. But, while in worms, serotonin boosts lead to increased eating and fat loss, in humans, serotonin bumps are known to prompt less eating, which in turn leads to a decrease in fat tissue.

Nevertheless, Ashrafi and his team concluded that their analysis of worms offers clear cross-species indications that whether one is fat or thin is not a pure calculation of caloric intake but rather a complex result of multiple nervous system calculations based on both genetic and environmental factors.

"We don't know the real answer yet," Ashrafi said. "We are just beginning to scratch the surface. But I think chances are pretty good that this is something likely to be operating in most organisms. And, the fact is that the consumption of food is a very dynamic process, with a strong genetic component that clearly goes beyond the question of diet."

Alice H. Lichtenstein, director of the Cardiovascular Nutrition Lab at Tufts University's USDA Human Nutrition Research Center in Boston, cautioned that attributing weight and fat gain to environmental or genetic sources can be tricky and complicated.

"We clearly know that the nervous system will impact on food intake, and the exploration of genetic predispositions toward weight gain and obesity is not new," she said. "In fact, there has been an immense amount of effort over a long period of time devoted toward sorting this out."

"This study probably adds a new dimension to the ongoing work," added Lichtenstein, immediate past chair of the American Heart Association's nutrition committee. "But the issue is really very, very complex. So, while I think it's important to bring up all the different possibilities of what can impact on weight, it's certainly going to take a long time to sort it all out."

More information

To learn more about the causes of obesity, visit the U.S. Centers for Disease Control and Prevention.

SOURCES: Kaveh Ashrafi, Ph.D., assistant professor, department of physiology and Diabetes Center, University of California, San Francisco; Alice H. Lichtenstein, D.Sc., director, Cardiovascular Nutrition Lab, Gershoff Professor of Nutrition, USDA Human Nutrition Research Center, Tufts University, Boston, and immediate past chair, nutrition committee, American Heart Association; June 2008, Cell Metabolism
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