Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle.
Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle.
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DOI：
10.4103/2230-8210.105573
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发表时间：
2012-12
影响因子：
--
通讯作者：
Okamoto S
中科院分区：
文献类型：
--
作者：
Minokoshi Y;Toda C;Okamoto S
瘦素是由脂肪细胞分泌的一种激素，在调节食物摄入、能量消耗和神经内分泌功能中起关键作用。许多证据表明，瘦素在啮齿动物和人类的外周组织中调节糖和脂质代谢，而不依赖于胰岛素效应。已经显示瘦素改善脂肪营养不良患者和啮齿动物中的糖尿病表型。此外，瘦素抑制啮齿类动物胰岛素缺乏型糖尿病中严重的、进行性的葡萄糖代谢损害的发展。我们发现瘦素在体内增加大鼠和小鼠骨骼肌的葡萄糖摄取和脂肪酸氧化。瘦素通过下丘脑-交感神经系统轴和β-肾上腺素能机制增加骨骼肌的葡萄糖摄取，而瘦素通过AMP激活的蛋白激酶（AMPK）刺激肌肉中的脂肪酸氧化。瘦素诱导的脂肪酸氧化导致肌肉中脂质积累减少，这可导致称为“脂毒性”的功能障碍。AMPK的激活通过瘦素对肌肉的直接作用以及通过内侧下丘脑-交感神经系统和α-肾上腺素能机制发生。因此，瘦素在骨骼肌葡萄糖和脂肪酸代谢的调节中起重要作用。
Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulation of food intake, energy expenditure, and neuroendocrine function. Several lines of evidences indicate that independent of the anorexic effect, leptin regulates glucose and lipid metabolism in peripheral tissues in rodents and humans. It has been shown that leptin improves the diabetes phenotype in lipodystrophic patients and rodents. Moreover, leptin suppresses the development of severe, progressive impairment of glucose metabolism in insulin-deficient diabetes in rodents. We found that leptin increases glucose uptake and fatty acid oxidation in skeletal muscle in rats and mice in vivo. Leptin increases glucose uptake in skeletal muscle via the hypothalamic–sympathetic nervous system axis and β-adrenergic mechanism, while leptin stimulates fatty acid oxidation in muscle via AMP-activated protein kinase (AMPK). Leptin-induced fatty acid oxidation results in the decrease of lipid accumulation in muscle, which can lead to functional impairments called as “lipotoxicity.” Activation of AMPK occurs by direct action of leptin on muscle and through the medial hypothalamus–sympathetic nervous system and α-adrenergic mechanism. Thus, leptin plays an important role in the regulation of glucose and fatty acid metabolism in skeletal muscle.