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Pulling the String on Yo-Yo Weight Gain

Mice that lost weight and then gained back more than they lost maintained an obesity-type microbiome that affected biochemicals involved in either burning or adding fat--suggesting interventions.

 

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“We focus on what is called recurrent obesity or yo-yo obesity, which is a feature which affects close to 80 percent of all overweight individuals worldwide.”

Eran Elinav of the Weitzmann Institute of Science in Israel.

“This is the phenomenon in which we gain weight and then we go on a successful diet, but within 12 months we go back to our original weight. And we even gain more weight from cycle to cycle. So this is called recurrent obesity.”


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But Elinav may have taken a step toward getting a handle on that frustrating post-diet pound packing that leaves people heavier than when they started. He spoke February 17th at the annual meeting of the American Association for the Advancement of Science in Boston.

“We developed a few models in mice, which feature this exact pattern of recurrent exaggerated obesity…following cycles of obesity and successful dieting. And what we found was that the one important determinant which drives this exaggerated weight regain tendency is a persistent alteration of the composition and function of our gut microbiome following a successful dieting. In other words, we diet and we normalize all of our metabolic parameters after we successfully diet…”

But we still can maintain the microbial profile—and function—that we had before losing the weight. So Elinav’s team did a detailed analysis of the biochemistry going on within the mice.

“And we came across two molecules in mice which are from the flavonoid family. And basically these molecules signal to the host adipose tissue telling it to extract more heat and to gain less fat.”

The molecules, called apigenin and naringenin, get degraded in the presence of the obesity-related microbiome. [Christoph A. Thaiss et al., Persistent microbiome alterations modulate the rate of post-dieting weight regain, in Nature]

“And when they are low the fat doesn’t get this signal and then weight regain occurs. So in this particular case the intervention which we’ve used is to replenish these two missing or these two degraded molecules through administration in food and their drinking water. And when we brought them back to physiological levels we completely abolished this tendency for an exaggerated weight regain.

“Now extrapolating to humans, if this is true in humans and we would discover these or maybe other molecules which are depleted or in excess…an intervention which would supplement them or block their downstream signaling would potentially be helpful in this regard.”

—Steve Mirsky

[The above text is a transcript of this podcast.]

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