Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding

Publication date: Available online 21 June 2018
Source:Cell Metabolism
Author(s): Yann Ravussin, Ethan Edwin, Molly Gallop, Lumei Xu, Alberto Bartolomé, Michael J. Kraakman, Charles A. LeDuc, Anthony W. Ferrante
Weight is defended so that increases or decreases in body mass elicit responses that favor restoration of one's previous weight. While much is known about the signals that respond to weight loss and the central role that leptin plays, the lack of experimental systems studying the overfed state has meant little is known about pathways defending against weight gain. We developed a system to study this physiology and found that overfed mice defend against increased weight gain with graded anorexia but, unlike weight loss, this response is independent of circulating leptin concentration. In overfed mice that are unresponsive to orexigenic stimuli, adipose tissue is transcriptionally and immunologically distinct from fat of ad libitum-fed obese animals. These findings provide evidence that overfeeding-induced obesity alters adipose tissue and central responses in ways that are distinct from ad libitum obesity and activates a non-leptin system to defend against weight gain.

Graphical abstract

Teaser

Following overfeeding, mice decrease food intake and return to their previous weight. The signal or set of signals that underlie this response is not known. Ravussin et al. have developed a model to investigate overfeeding in mice and provide evidence for a leptin-independent system that defends against body weight gain.


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