Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation.-猫眼课题宝

DOI：

10.1016/j.cmet.2006.02.001

发表时间：

2006-03

期刊：

Cell metabolism

影响因子：

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Tetsuya Yamada;H. Katagiri;Y. Ishigaki;T. Ogihara;Junta Imai;Kenji Uno;Yutaka Hasegawa;Junhong Gao;H. Ishihara;A. Niijima;H. Mano;H. Aburatani;T. Asano;Y. Oka

腹内脂肪堆积参与代谢综合征的发展，而代谢综合征与胰岛素和瘦素抵抗有关。我们在这里表明，在附睾脂肪（Epi）中，极低水平的解偶联蛋白1 （UCP1）的异位表达逆转了胰岛素和瘦素抵抗。在饮食诱导和遗传性肥胖小鼠模型中，Epi中UCP1的表达改善了葡萄糖耐量并减少了食物摄入量。相比之下，瘦素受体突变小鼠Epi中UCP1的表达没有改变食物摄入量，尽管它显著降低了血糖和胰岛素水平。因此，下咽诱导需要瘦素信号，而胰岛素敏感性的改善似乎与瘦素无关。在野生型小鼠中，附睾局部神经解剖或药物传入阻滞使食物摄入的减少变得迟钝，这表明来自腹内脂肪组织的传入神经信号通过调节下丘脑瘦素敏感性来调节食物摄入。这些新的信号是代谢综合征的潜在治疗靶点。

Intra-abdominal fat accumulation is involved in development of the metabolic syndrome, which is associated with insulin and leptin resistance. We show here that ectopic expression of very low levels of uncoupling protein 1 (UCP1) in epididymal fat (Epi) reverses both insulin and leptin resistance. UCP1 expression in Epi improved glucose tolerance and decreased food intake in both diet-induced and genetically obese mouse models. In contrast, UCP1 expression in Epi of leptin-receptor mutant mice did not alter food intake, though it significantly decreased blood glucose and insulin levels. Thus, hypophagia induction requires a leptin signal, while the improved insulin sensitivity appears to be leptin independent. In wild-type mice, local-nerve dissection in the epididymis or pharmacological afferent blockade blunted the decrease in food intake, suggesting that afferent-nerve signals from intra-abdominal fat tissue regulate food intake by modulating hypothalamic leptin sensitivity. These novel signals are potential therapeutic targets for the metabolic syndrome.

Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation.

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