State Key Laboratory of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing 100193, China.
BMB Rep. 2010 Feb;43(2):140-5. doi: 10.5483/bmbrep.2010.43.2.140.
The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regulation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramatically increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-alpha (C/EBP-alpha) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regulatory-element-binding protein (SREBP)-1c protein were induced on day 4. Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Collectively, our findings suggest that the adipogenic differentiation of porcine muscle satellite cells and a succeeding extensive adipogenesis, which is triggered by high glucose, is initiated by the mTOR signal pathway through the activation of SREBP-1c protein. This process is previously uncharacterized and suggests a cellular mechanism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.
本研究旨在探讨哺乳动物雷帕霉素靶蛋白（mTOR）信号通路是否参与调控猪肌肉卫星细胞的高糖诱导的肌内脂肪生成。高葡萄糖（25mM）在 10 天的成脂分化期间显著增加了细胞内的脂质积累。在 10 天的过程中，CCAAT/增强子结合蛋白-α（C/EBP-α）和脂肪酸合酶（FAS）蛋白的表达逐渐增强，而 mTOR 磷酸化和固醇调节元件结合蛋白-1c（SREBP-1c）蛋白在第 4 天被诱导。此外，雷帕霉素抑制 mTOR 活性导致 SREBP-1c 蛋白表达和细胞内脂肪生成减少。综上所述，我们的研究结果表明，猪肌肉卫星细胞的成脂分化以及随后的高葡萄糖诱导的广泛脂肪生成是由 mTOR 信号通路通过激活 SREBP-1c 蛋白启动的。这一过程以前尚未被描述过，表明在 2 型糖尿病中，细胞机制可能参与了骨骼肌中的异位脂质沉积。
