SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity.
SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity.
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DOI：
10.1016/j.cmet.2010.05.010
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发表时间：
2010-07-07
期刊：
影响因子：
29
通讯作者：
Coppari R
中科院分区：
文献类型：
--
作者：
Ramadori G;Fujikawa T;Fukuda M;Anderson J;Morgan DA;Mostoslavsky R;Stuart RC;Perello M;Vianna CR;Nillni EA;Rahmouni K;Coppari R
喂食高热量（HC）饮食会导致严重的代谢失衡，包括肥胖。了解防止体重过度增加的机制对于制定有效的抗肥胖策略至关重要。在这里，我们表明，缺乏烟酰胺腺苷二核苷酸（NAD+）依赖性脱乙酰基酶SIRT 1在前阿黑皮素（POMC）神经元引起过敏的饮食诱导的肥胖，由于减少能量消耗。在突变小鼠中，瘦素正确参与POMC神经元中的磷酸肌醇3-激酶（PI 3 K）信号传导并引起性腺周围白色脂肪组织（WAT）重塑的能力严重受损。此外，电生理和组织形态分子分析表明，选择性减少交感神经活动和棕色脂肪样特征的突变小鼠的性腺周围WAT，这表明生理上的重要作用POMC神经元控制这个内脏脂肪仓库。总之，我们的研究结果提供了直接的遗传证据，POMC神经元中的SIRT 1是针对饮食诱导的肥胖的正常自主适应所必需的。
Feeding on high-calorie (HC) diets induces serious metabolic imbalances, including obesity. Understanding the mechanisms against excessive body weight gain is critical for developing effective anti-obesity strategies. Here, we show that lack of nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase SIRT1 in pro-opiomelanocortin (POMC) neurons causes hypersensitivity to diet-induced obesity due to reduced energy expenditure. The ability of leptin to properly engage the phosphoinositide 3-kinase (PI3K) signaling in POMC neurons and elicit remodeling of perigonadal white adipose tissue (WAT) is severely compromised in mutant mice. Also, electrophysiological and histomorphomolecular analyses indicate a selective reduction in sympathetic nerve activity and brown-fat-like characteristics in perigonadal WAT of mutant mice; suggesting a physiologically important role for POMC neurons in controlling this visceral fat depot. In summary, our results provide direct genetic evidence that SIRT1 in POMC neurons is required for normal autonomic adaptations against diet-induced obesity.
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