DHA at nutritional doses restores insulin sensitivity in skeletal muscle by preventing lipotoxicity and inflammation
DHA at nutritional doses restores insulin sensitivity in skeletal muscle by preventing lipotoxicity and inflammation
复制标题
DOI：
10.1016/j.jnutbio.2015.04.003
复制
发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Morio, Beatrice
中科院分区：
文献类型：
--
作者：
Capel, Frederic;Acquaviva, Cecile;Morio, Beatrice
在胰岛素刺激下，骨骼肌在控制全身葡萄糖处理中起着重要作用。过多的脂肪酸供应会引发细胞和分子紊乱，导致脂肪中毒、炎症、线粒体功能障碍、胰岛素反应受损和葡萄糖摄取减少。本研究旨在分析长链多不饱和n-3脂肪酸二十二碳六烯酸（DHA）在与营养补充相适应的剂量下对骨骼肌胰岛素抵抗、脂肪毒性和炎症的预防作用。DHA （30 μ M）通过降低蛋白激酶C (PKC)-theta的激活，恢复细胞酰基肉碱谱，胰岛素依赖性AKT磷酸化和葡萄糖摄取，抑制棕榈酸（500 μ M）暴露的C2C12肌管的胰岛素抵抗。此外，DHA可能通过抑制p38 MAP激酶和c-Jun氨基末端激酶，保护C2C12肌管免受棕榈酸酯或脂多糖诱导的Ptgs2、白细胞介素6和肿瘤坏死因子α mRNA水平的升高。在喂食高胆固醇-高蔗糖饮食的LDLR -/-小鼠中，补充高达每日能量摄入2%的DHA增强了胰岛素依赖性AKT磷酸化，并降低了骨骼肌中PKC-theta的激活。因此，生理剂量的DHA通过防止脂肪毒性和炎症参与肌肉脂质和葡萄糖代谢的调节。(C) 2015爱思唯尔公司版权所有。
Skeletal muscle plays a major role in the control of whole body glucose disposal in response to insulin stimulus. Excessive supply of fatty acids to this tissue triggers cellular and molecular disturbances leading to lipotoxicity, inflammation, mitochondrial dysfunctions, impaired insulin response and decreased glucose uptake. This study was conducted to analyze the preventive effect of docosahexaenoic acid (DHA), a long-chain polyunsaturated n-3 fatty acid, against insulin resistance, lipotoxicity and inflammation in skeletal muscle at doses compatible with nutritional supplementation. DHA (30 mu M) prevented insulin resistance in C2C12 myotubes exposed to palmitate (500 mu M) by decreasing protein kinase C (PKC)-theta activation and restoring cellular acylcarnitine profile, insulin-dependent AKT phosphorylation and glucose uptake. Furthermore, DHA protected C2C12 myotubes from palmitate- or lipopolysaccharide-induced increase in Ptgs2, interleukin 6 and tumor necrosis factor-alpha mRNA level, probably through the inhibition of p38 MAP kinase and c-Jun amino-terminal kinase. In LDLR -/- mice fed a high-cholesterol-high-sucrose diet, supplementation with DHA reaching up to 2% of daily energy intake enhanced the insulin-dependent AKT phosphorylation and reduced the PKC-theta activation in skeletal muscle. Therefore, DHA used at physiological doses participates in the regulation of muscle lipid and glucose metabolisms by preventing lipotoxicity and inflammation. (C) 2015 Elsevier Inc. All rights reserved.