p75 Neurotrophin Receptor Regulates Energy Balance in Obesity.
p75 Neurotrophin Receptor Regulates Energy Balance in Obesity.
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DOI：
10.1016/j.celrep.2015.12.028
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发表时间：
2016-01-12
期刊：
影响因子：
8.8
通讯作者：
Akassoglou K
中科院分区：
文献类型：
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作者：
Baeza-Raja B;Sachs BD;Li P;Christian F;Vagena E;Davalos D;Le Moan N;Ryu JK;Sikorski SL;Chan JP;Scadeng M;Taylor SS;Houslay MD;Baillie GS;Saltiel AR;Olefsky JM;Akassoglou K
肥胖和代谢综合征反映了控制能量稳态的分子途径的失调。本研究表明，在高脂肪饮食（HFD）中，肥胖小鼠的p75神经营养因子受体（p75NTR）控制着能量消耗。尽管食物摄入量没有变化，但p75ntr缺失的小鼠免受hfd诱导的肥胖的影响，并且由于能量消耗的增加而保持苗条，没有发生胰岛素抵抗或肝脏脂肪变性。p75NTR直接与蛋白激酶A （PKA）的催化亚基相互作用，调节脂肪细胞中的cAMP信号，导致脂肪分解和产热减少。脂肪细胞特异性消耗p75NTR或将p75NTR缺失的白色脂肪组织（WAT）移植到喂食HFD的野生型小鼠中，可以防止体重增加和胰岛素抵抗。我们的研究结果表明，从p75NTR到cAMP/PKA的信号调节能量平衡，并提示神经营养因子受体信号的非神经元功能可能是治疗肥胖和代谢综合征的新靶点。
Obesity and metabolic syndrome reflect the dysregulation of molecular pathways that control energy homeostasis. Here we show that upon high-fat diet (HFD), the p75 neurotrophin receptor (p75NTR) controls energy expenditure in obese mice. Despite no changes in food intake, p75NTR-null mice were protected from HFD-induced obesity and remained lean due to increased energy expenditure, without developing insulin resistance or liver steatosis. p75NTR directly interacts with the catalytic subunit of protein kinase A (PKA) and regulates cAMP signaling in adipocytes, leading to decreased lipolysis and thermogenesis. Adipocyte-specific depletion of p75NTR or transplantation of p75NTR-null white adipose tissue (WAT) into wild-type mice fed a HFD protected against weight gain and insulin resistance. Our results reveal that signaling from p75NTR to cAMP/PKA regulates energy balance and suggest that non-neuronal functions of neurotrophin receptor signaling could be a new target for treating obesity and the metabolic syndrome.