Adipokines as regulators of muscle metabolism and insulin sensitivity
Adipokines as regulators of muscle metabolism and insulin sensitivity
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DOI：
10.1139/h09-037
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发表时间：
2009-06-01
影响因子：
3.4
通讯作者：
Dyck, David J.
中科院分区：
文献类型：
--
作者：
Dyck, David J.
骨骼肌是负责胰岛素刺激的葡萄糖处置的最大组织。然而，确定过量的身体脂肪和骨骼肌胰岛素敏感性受损之间的联系一直很困难。几种脂肪源性细胞因子（脂肪因子）与胰岛素敏感性受损有关，而脂肪因子如瘦素和脂联素则具有胰岛素增敏作用。瘦素和脂联素已被证明可以增加脂肪酸（FA）氧化和减少甘油三酯在肌肉中的储存，这可以部分解释这些细胞因子的胰岛素增敏作用。最近的证据强烈暗示增加本地化的FA转运蛋白的质膜（PM）的肌内脂质的积累与高脂肪饮食和肥胖症的一个重要因素。也许令人惊讶的是，相对较少的注意力已经支付给胰岛素增敏化合物，如瘦素和脂联素，以减少丰富的FA转运蛋白在PM中，从而减少脂质积累的能力。在这两种脂肪因子的情况下，也有证据表明，在肥胖期间，对它们刺激骨骼肌中FA氧化的能力的抵抗。我们最近的一项研究表明，这种发展可能非常迅速（即，几天内），并且在导致胰岛素抵抗的脂质摄取和积累增加之前。值得注意的是，瘦素抵抗可以通过啮齿动物的饮食和训练来调节。进一步的研究检查瘦素和脂联素抵抗的发展的潜在机制是必要的。
Skeletal muscle is the largest tissue responsible for the insulin-stimulated disposal of glucose. However, identifying the link between excess body fat and impaired insulin sensitivity in skeletal muscle has been difficult. Several adipose-derived cytokines (adipokines) have been implicated in the impairment of insulin sensitivity, while adipokines such as leptin and adiponectin exert an insulin-sensitizing effect. Leptin and adiponectin have each been shown to increase fatty acid (FA) oxidation and decrease triglyceride storage in muscle, which may explain, in part, the insulin-sensitizing effect of these cytokines. Recent evidence strongly implicates an increased localization of the FA transporters to the plasma membrane (PM) as an important factor in the accumulation of intramuscular lipids with high-fat diets and obesity. Perhaps suprisingly, relatively little attention has been paid to the ability of insulin-sensitizing compounds, such as leptin and adiponectin, to decrease the abundance of FA transporters in the PM, thereby decreasing lipid accumulation. In the case of both adipokines, there is also evidence that a resistance to their ability to stimulate FA oxidation in skeletal muscle develops during obesity. One of our recent studies indicates that this development can be very rapid (i.e., within days), and precedes the increase in lipid uptake and accumulation that leads to insulin resistance. It is noteworthy that leptin resistance can be modulated by both diet and training in rodents. Further studies examing the underlying mechanisms of the development of leptin and adiponectin resistance are warranted.