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首页> 外文期刊>Journal of cellular physiology. >SCD1 regulates the AMPK/SIRT1 pathway and histone acetylation through changes in adenine nucleotide metabolism in skeletal muscle
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SCD1 regulates the AMPK/SIRT1 pathway and histone acetylation through changes in adenine nucleotide metabolism in skeletal muscle

机译：SCD1调控AMPK / SIRT1通路和组蛋白乙酰化作用通过腺嘌呤核苷酸的变化在骨骼肌代谢

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摘要

Stearoyl-CoA desaturase (SCD) is a rate-limiting enzyme that catalyzes the synthesis of monounsaturated fatty acids. It plays an important role in regulating skeletal muscle metabolism. Lack of the SCD1 gene increases the rate of fatty acid β-oxidation through activation of the AMP-activated protein kinase (AMPK) pathway and the upregulation of genes that are related to fatty acid oxidation. The mechanism of AMPK activation under conditions of SCD1 deficiency has been unclear. In the present study, we found that the ablation/inhibition of SCD1 led to AMPK activation in skeletal muscle through an increase in AMP levels whereas muscle-specific SCD1 overexpression decreased both AMPK phosphorylation and the adenosine monopho-sphate/adenosine triphosphate (AMP/ATP) ratio. Changes in AMPK phosphorylation that were caused by SCD1 down- and upregulation affected NAD+ levels following changes in NAD+-dependent deacetylase sirtuin-1 (SIRT1) activity and histone 3 (H3K9) acetylation and methylation status. Moreover, mice with muscle-targeted overexpression of SCD1 were more susceptible to high-fat diet-induced lipid accumulation and the development of insulin resistance compared with wild-type mice. These data show that SCD1 is involved in nucleotide (ATP and NAD+) metabolism and suggest that the SCD1-dependent regulation of muscle steatosis and insulin sensitivity are mediated by cooperation between AMPK- and SIRT1-regulated pathways. Altogether, the present study reveals a novel mechanism that links SCD1 with the maintenance of metabolic homeostasis and insulin sensitivity in skeletal muscle.
机译：Stearoyl-CoA desaturase (SCD)是一种病原酶催化合成的单不饱和脂肪酸。重要的作用在调节骨骼肌新陈代谢。通过激活的脂肪酸β氧化活化蛋白激酶(AMPK)通路和基因的upregulation与脂肪酸氧化有关。SCD1 AMPK活化条件下缺乏一直不清楚。研究中,我们发现烧蚀/抑制SCD1导致骨骼肌AMPK活化而通过增加安保水平阳性SCD1超表达减少AMPK磷酸化和腺苷monopho-sphate /三磷酸腺苷(AMP / ATP)比率。SCD1下来,upregulation造成的影响NAD +端依赖NAD +后水平变化和脱乙酰酶sirtuin-1 (SIRT1)活动组蛋白3 (H3K9)乙酰化和甲基化的地位。超表达SCD1都更容易高脂肪食源性和脂质积累胰岛素抵抗与发展野生型老鼠。参与核苷酸(ATP和NAD +)新陈代谢并表明SCD1-dependent监管肌肉脂肪变性和胰岛素敏感性由AMPK和合作SIRT1-regulated通路。研究揭示了一个新颖的机制,SCD1的链接与代谢体内平衡和维护在骨骼肌的胰岛素敏感性。

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