Mice Losing Weight With Less Exercise?

What if there was a pill that would allow you to add lean muscle mass and lower your cholesterol and insulin levels, all while chowing down on your favorite high-fat, high-sugar foods?

Scripps Research Institute scientists in Florida may have done just that — in mice. The scientists have crafted a pair of synthetic molecules that cause them to lose weight, exercise more, and normalize their blood sugar by tinkering with the “clock” that controls a mouse’s metabolism.

The research, published in Nature online, opens the door for new drugs to treat obesity, cardiovascular disease, and sleep disorders, says Thomas Burris, director of the Scripps Center for Diabetes and Metabolic Diseases.

Since 2005, Burris and his team have been researching proteins called REV-ERB alpha and beta, which regulate activity in the suprachiasmatic nucleus, a rice grain-sized structure in the brain’s hypothalamus that functions like a master clock and sets the body’s circadian rhythms. The team developed molecules that activate the REV-ERB proteins, and showed that depending when they are administered, these proteins can alter when and how much mice sleep and exercise.

In an experiment, normal mice were put on a high-fat diet similar to a typical westernized human diet — and they gained weight. When the mice were given the clock-regulating drug twice a day for 12 days, they lost body fat — while eating the same diet.

“They’re losing [fat] because they’re changing the amount of energy expenditure,” he says. The mice actually exercised a bit less, but their muscles burned sugars and fats more efficiently, Burris says. The mice’s insulin and cholesterol levels also improved (cholesterol down by 50 percent!).

The lab has already developed more robust versions of the new molecules, but use in humans could be a ways off. No one knows if the synthetic compounds created uncomfortable side effects for the mice, something that could be a deal-killer in people.

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