Internal clock tied to gaining weight-

A.J. HOSTETLER / Media General News Service
Published: May 22, 2007

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  Diet and weight loss

Mice lacking a gene involved in regulating the daily biological clock stayed trim even when fed a high-fat diet, say University of Virginia researchers.

Body clocks, or circadian rhythms, are those innate rhythms in plants and animals, including humans, that regulate basic functions such as sleep, hormone levels and internal temperatures. They run on a 24-hour-or-so cycle, kept on track by internal "clocks."

Over the past decade, biologists have uncovered several genes in mammals that make up the body clocks' inner workings. One such gene, called Nocturnin, occurs in mice and humans. The gene's protein levels fluctuate throughout the body's tissues and organs over the course of the day, especially in the liver, which is involved in metabolism.

Scientists at U.Va., working with a researcher at the Medical College of Wisconsin, decided to investigate what happens to the body without Nocturnin. Their results could shed light on how disruptions in biological clocks exacerbate the problem of obesity and perhaps ways to combat it.

"Irregular and hectic lifestyles that are prevalent in the contemporary world may disrupt the circadian clock and change the susceptibility to high-fat diets," the researchers wrote in this week's Proceedings of the National Academy of Sciences.

To examine Nocturnin's role in biological clocks and metabolism, the biologists created mice lacking the gene. Despite the alteration, they were healthy, could reproduce and had normal sleep cycles, said U.Va. graduate student Nicholas Douris. Douris and U.Va. circadian rhythm expert Carla Green were the lead authors of the report.

Groups of the two were put on a high-fat diet, what Douris called the equivalent of a "hot dogs, hamburgers, pizzas" human diet.

The diet lasted at least 100 days.

The normal mice quickly packed on the pounds, accumulating fat around their livers. Their altered counterparts stayed relatively trim with little fat accumulating around their livers. They weren't eating any less and were even less active, yet weighed about 20 percent less than the other mice, according to Douris.

The work suggests that Nocturnin is not a key component of the body clock, but it may indirectly regulate other genes related to storing fat or metabolism. Douris, Green and Wisconsin co-author Joseph Besharse have filed for a patent related to their research.

A.J. Hostetler is a staff writer at the Richmond Times-Dispatch.