Independent and Additive Effects of Central POMC and Leptin Pathways on Murine Obesity

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Science  28 Nov 1997:
Vol. 278, Issue 5343, pp. 1641-1644
DOI: 10.1126/science.278.5343.1641

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The lethal yellow(AY/a) mouse has a defect in proopiomelanocortin (POMC) signaling in the brain that leads to obesity, and is resistant to the anorexigenic effects of the hormone leptin. It has been proposed that the weight-reducing effects of leptin are thus transmitted primarily by way of POMC neurons. However, the central effects of defective POMC signaling, and the absence of leptin, on weight gain in double-mutant lethal yellow(AY/a) leptin-deficient (lepob/lep ob) mice were shown to be independent and additive. Furthermore, deletion of the leptin gene restored leptin sensitivity toAY/a mice. This result implies that in the AY/a mouse, obesity is independent of leptin action, and resistance to leptin results from desensitization of leptin signaling.

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