Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Metabolism. 2011 Nov;60(11):1598-609. doi: 10.1016/j.metabol.2011.04.002. Epub 2011 May 31.
Although resveratrol (RES) is implicated in the regulation of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle lipid transportation and lipid oxidation of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle lipid transportation was studied in rats fed a normal diet, an HFD, and an HFD with intervention of RES for 8 weeks. Citrate synthase (CS), electron transport chain (ETC) activities, and several enzymes for mitochondrial β-oxidation were assessed in SS and IMF mitochondria from tibialis anterior muscle. The HFD-fed rats exhibited obvious systemic and skeletal muscle IR as well as intramuscular lipid accumulation. SIRT1 activity and expression of genes related to mitochondrial biogenesis were greatly declined, whereas the gene for lipid transportation, FAT/CD36, was upregulated (P < .05). Subsarcolemmal but not IMF mitochondria displayed lower CS, ETC, and β-oxidation activities. By contrast, RES treatment protected rats against diet-induced intramuscular lipid accumulation and IR, increased SIRT1 activity and mitochondrial biogenesis, and reverted the decline in SS mitochondrial CS and ETC activities. Importantly, although expression of FAT/CD36 was increased (11%, P < .05), activities of SS mitochondrial β-oxidation enzymes were largely enhanced (41%~67%, P < .05). This study suggests that RES ameliorates insulin sensitivity consistent with an improved balance between skeletal muscle lipid transportation and SS mitochondrial β-oxidation in HFD rats.
尽管白藜芦醇（RES）被认为参与了调节啮齿动物的胰岛素敏感性，但这种作用的确切机制仍不清楚。因此，我们试图研究 RES 如何影响高脂肪饮食（HFD）诱导的胰岛素抵抗（IR）大鼠的骨骼肌脂质转运和亚肌小节（SS）和肌间纤维（IMF）线粒体群的脂质氧化。8 周后，研究了正常饮食、HFD 喂养和 HFD 干预 RES 的大鼠的全身和骨骼肌胰岛素敏感性以及与线粒体生物发生和骨骼肌脂质转运相关的几个基因的表达。从比目鱼肌中评估 SS 和 IMF 线粒体中的柠檬酸合酶（CS）、电子传递链（ETC）活性和几种线粒体β-氧化酶。HFD 喂养的大鼠表现出明显的全身和骨骼肌胰岛素抵抗以及肌肉内脂质堆积。SIRT1 活性和与线粒体生物发生相关的基因表达显著下降，而脂质转运基因 FAT/CD36 上调（P<0.05）。SS 但不是 IMF 线粒体显示出较低的 CS、ETC 和β-氧化活性。相比之下，RES 治疗可防止饮食引起的肌肉内脂质积累和 IR，增加 SIRT1 活性和线粒体生物发生，并逆转 SS 线粒体 CS 和 ETC 活性的下降。重要的是，尽管 FAT/CD36 的表达增加（11%，P<0.05），但 SS 线粒体β-氧化酶的活性大大增强（41%~67%，P<0.05）。这项研究表明，RES 可改善胰岛素敏感性，与 HFD 大鼠骨骼肌脂质转运和 SS 线粒体β-氧化之间的平衡改善一致。
