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High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR

机译:高糖通过mTOR诱导猪肌肉卫星细胞分化和成脂

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摘要

The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regu-lation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramati-cally increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-a (C/EBP-α) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regu-latory-element-binding protein (SREBP)-1c protein were in-duced on day 4. Moreover, inhibition of mTOR activity by ra-pamycin resulted in a reduction of SREBP-lc protein expre-ssion and adipogenesis in cells. Collectively, our findings sug-gest that the adipogenic differentiation of porcine muscle satel-lite 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 proc-ess is previously uncharacterized and suggests a cellular mech-anism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.
机译:本研究调查了雷帕霉素(mTOR)信号通路的哺乳动物目标是否参与调节猪葡萄糖卫星细胞中高糖诱导的肌内脂肪形成。在10天的成脂分化期中,高葡萄糖(25 mM)戏剧性地增加了细胞内细胞内脂质的积累。在10天的时间内,CCAAT /增强子结合蛋白-α(C /EBP-α)和脂肪酸合酶(FAS)的表达逐渐增强,而mTOR磷酸化和固醇调节元素结合蛋白(SREBP) )-1c蛋白在第4天被诱导。此外,雷帕霉素对mTOR活性的抑制导致细胞中SREBP-lc蛋白表达和脂肪形成的减少。总的来说,我们的发现表明,猪肌肉卫星薄层细胞的成脂分化和由高葡萄糖触发的后续广泛的成脂作用,是通过激活SREBP-1c蛋白的mTOR信号途径引发的。该过程以前没有特征,提示在2型糖尿病期间,细胞机制可能与骨骼肌中异位脂质沉积有关。

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