Mice given metabolite succinate found to lose weight by turning up the heat

A team of researchers with members from institutions across the U.S. and Canada has found that giving the metabolite succinate to mice fed a high-fat diet prevented obesity. In their paper published in the journal Nature, the group explains how they came to study the metabolite and why it helped prevent obesity in mice. Sheng Hui and Joshua Rabinowitz with Princeton University offer a News & Views piece on the work done by the team in the same journal issue. They also discuss the possibility of giving the metabolite to humans as a possible treatment for obesity.

As the researchers note, people and other mammals gain weight when they consume energy sources at a faster rate than they burn them. That energy is stored in white fat. But, as they also note, humans and other mammals also have another type of fat—brown fat—which, instead of storing energy, actually burns fuel sources and expends heat in the process. Burning such fuel, they further note, rather than storing it, prevents weight gain. Prior research has shown that the body alerts brown fat to burn fuel when it gets cold, in the form of shivering. But the mechanism by which this occurs has been a mystery. In this new effort, the researchers have identified the mechanism, and in so doing may have found a way to combat obesity.

Noting that brown fat starts burning more fuel when muscles start to shiver, the researchers looked for changes in brown fat cells when it happens. In so doing, they discovered an increase in the metabolite succinate. They discovered that as the body gets cold, muscles shiver and their cells release succinate into the bloodstream. The brown fat cells absorb the succinate causing them to burn more fuel, producing heat.

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