Independent and additive effects of central POMC and leptin pathways on murine obesity
Independent and additive effects of central POMC and leptin pathways on murine obesity
复制标题
DOI：
10.1126/science.278.5343.1641
复制
发表时间：
1997-11-28
期刊：
影响因子：
56.9
通讯作者：
Cone, RD
中科院分区：
文献类型：
--
作者：
Boston, BA;Blaydon, KM;Cone, RD
致死性黄色（A（Y）/a）小鼠在大脑中具有导致肥胖的阿黑皮素原（POMC）信号传导缺陷，并且对激素瘦素的促肥胖作用具有抗性。有人提出，瘦素的减肥作用主要通过POMC神经元传递。然而，在双突变致死性黄色（A（Y）/a）leptin缺陷（lep（ob）/lep（ob））小鼠中，POMC信号传导缺陷和leptin缺乏对体重增加的中枢作用被证明是独立的和累加的。此外，缺失leptin基因恢复了A（Y）/a小鼠的leptin敏感性。这一结果表明，在A（Y）/a小鼠中，肥胖与瘦素作用无关，对瘦素的抵抗是瘦素信号转导脱敏的结果。
The lethal yellow (A(Y)/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 (A(Y)/a) leptin-deficient (lep(ob)/lep(ob)) mice were shown to be independent and additive, Furthermore, deletion of the leptin gene restored leptin sensitivity to A(Y)/a mice. This result implies that in the A(Y)/a mouse, obesity is independent of leptin action, and resistance to leptin results from desensitization of leptin signaling.