内科学
骨骼肌
内分泌学
脂毒性
胰岛素抵抗
脂滴包被蛋白
脂滴
二酰甘油激酶
生物
脂质代谢
激素敏感脂肪酶
脂肪组织
胰岛素
化学
脂解
细胞生物学
磷酸化
医学
蛋白激酶C
作者
Madeleen Bosma,Matthijs K. C. Hesselink,Lauren M. Sparks,Silvie Timmers,Maria J. Ferraz,Frits Mattijssen,Denis van Beurden,Gert Schaart,Marc H. De Baets,Fons Verheyen,Sander Kersten,Patrick Schrauwen
出处
期刊:Diabetes
[American Diabetes Association]
日期:2012-10-16
卷期号:61 (11): 2679-2690
被引量:128
摘要
Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid (IMCL) storage exceeds intracellular needs and induces lipotoxic events, ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/adipose differentiation-related protein [ADRP]) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol (TAG) storage, marginally increased fatty-acid (FA) oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase in protein content of the subunits of the oxidative phosphorylation (OXPHOS) chain. Diacylglycerol levels were unchanged, whereas ceramide levels were increased. Despite the increased IMCL accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs toward TAG storage in LDs, thereby blunting lipotoxicity-associated insulin resistance.
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