Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans
Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans
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DOI：
10.1016/j.cmet.2005.09.002
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发表时间：
2005-10-01
期刊：
影响因子：
29
通讯作者：
Muoio, DM
中科院分区：
文献类型：
--
作者：
Hulver, MW;Berggren, JR;Muoio, DM
肥胖和2型糖尿病与脂质代谢异常以及肌细胞内甘油三酯的积累密切相关，但这些紊乱的根本原因尚不清楚。在此，我们表明，在极度肥胖的人的骨骼肌中，脂肪生成基因硬脂酰辅酶A去饱和酶1（SCD1）显著上调。SCD1是一种催化单不饱和脂肪酸合成的酶，其高表达和高活性与脂肪酸氧化率低、甘油三酯合成增加以及肌肉脂质的单不饱和程度增加相对应。与瘦的供体相比，从肥胖者获取的原代骨骼肌细胞中SCD1表达升高以及脂质分配异常仍然存在，这意味着这些特征可能是由表观遗传和/或遗传机制驱动的。在瘦的受试者的肌管中过表达人SCD1足以模拟肥胖表型。这些结果表明，骨骼肌中SCD1的高表达导致了脂质代谢异常和肥胖的进展。
Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.