Watch the Clock to Lose Weight

When we eat may be just as important as what we eat. A new study shows that mice that eat when they should be sleeping gain more weight than mice that eat at normal hours. Another study sheds light on why we pack on the pounds in the first place. Whether these studies translate into therapies that help humans beat obesity remains to be seen, but they give scientists clues about the myriad factors that they must take into account.

Uneven gains. Mice with an immunity gene knocked out gain less weight than normal mice, and their livers (inset) pack on less unsightly fat.

Observations of overnight workers have shown that eating at night disrupts metabolism and the hormones that signal we're sated. But no one had done controlled studies on this connection until now. Biologist Fred Turek of Northwestern University in Evanston, Illinois, and graduate student Deanna Arble examined the link between a high-fat diet and what time of day mice eat. A control group of six nocturnal mice ate their pellets (60% fat by calories, mostly lard) during the night. Another group of six ate the same meal during the day, Turek says, which disrupts their circadian rhythm--the body's normal 24-hour cycle.

After 6 weeks, the off-schedule mice weighed almost 20% more than the controls, Turek and Arble report today in Obesity, supporting the idea that consuming calories when you should be sleeping is harmful. Turek and Arble acknowledge that the disrupted mice ate a tad more and were a tad more sluggish, but the differences could not account for all of the weight gain.

In the second study, a different team of researchers investigated the link between weight and the immune system. Hundreds of genes seem to affect the accumulation of fat, but one that helps protect us from infection might help us lose weight with little effort, biochemist Alan Saltiel of the University of Michigan, Ann Arbor, and colleagues suggest today in Cell. The researchers tested the weight-adding abilities of a protein called IKKε, which is linked with obesity, diabetes, and chronic, low-level inflammation. For 3 months, the team fed six mice missing IKKε genes a diet of high-fat chow.

Because IKKε's main job is immune defense, Saltiel's team didn't expect to find weight differences between knockout mice and controls. But the knockout mice did gain significantly less. Best of all, the girth the animals did add was less harmful to their overall health. "The knockout mice don't gain as much weight but also don't get diabetes, don't get insulin resistance, and don't get accumulation of lipids on the liver," Saltiel says, all of which contribute to the suite of health problems associated with being overweight. Saltiel calls IKKε "an especially appealing drug target for the treatment of metabolic disease."

Tom Maniatis, a molecular biologist at Harvard University, praises the study but remains skeptical about any drug that would inhibit IKKε. He helped develop the mice used in the experiment and notes that they are vulnerable to the flu. He suspects that suppressing IKKε may help people with diabetes or obesity, "but the first time the swine flu comes along, that's it."

Researchers are also enthusiastic about the circadian rhythm paper. Frank Scheer, a neuroscientist at Harvard who studies sleep, was struck that "you could see something happening [to the disrupted mice] in the 1st week already. That's consistent with human studies where we found changes in just 3 days."

Together, the papers suggest that there's no simple answer to why people gain weight. Says Turek, "It's clearly not just calories in versus calories out."

By Sam Kean
ScienceNOW Daily News
3 September 2009


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