Research ArticleObesity

Cleavage of the leptin receptor by matrix metalloproteinase–2 promotes leptin resistance and obesity in mice

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Science Translational Medicine  22 Aug 2018:
Vol. 10, Issue 455, eaah6324
DOI: 10.1126/scitranslmed.aah6324

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Restoring leptin’s effects in obesity

Obesity is the most common metabolic disease in the developed world. Although obese individuals have increased plasma concentrations of the anorexigenic hormone leptin, they are refractory to its anorexigenic effect. Mazor et al. showed that, in rodents, obesity induced matrix metalloproteinase–2 (Mmp-2) activation in the hypothalamus. In turn, Mmp-2 activation reduced leptin-mediated signaling by promoting leptin receptor degradation. Mmp-2 deletion in the hypothalamus increased leptin receptor expression and reduced fat accumulation in mice fed a high-fat diet. The results suggest that targeting Mmp-2 might be an effective strategy for treating obesity by restoring the anorexigenic effects of leptin.