Chen Shiuan-Chih, Chen Pei-Yin, Wu Yu-Ling, Chen Ching-Wen, Chen Haw-Wen, Lii Chong-Kuei, Sun Hai-Lun, Liu Kai-Li
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan.
Food Funct. 2016 Jan;7(1):270-8. doi: 10.1039/c5fo00704f.
Intramuscular lipid accumulation results in inflammation, which is correlated with impaired insulin action in the skeletal muscle, an important organ for glucose uptake in the body. In this study, we explored the effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (AA), and long-chain polyunsaturated fatty acids (PUFAs) on palmitic acid (PA)-induced inflammatory responses and insulin resistance in C2C12 myotubes. The mRNA expression of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α in PA-treated myotubes was suppressed by these three test long-chain PUFAs. Moreover, the addition of long-chain PUFAs decreased PA-induced insulin resistance as evidenced by increases in phosphorylated AKT and glucose uptake. In PA-treated myotubes, long-chain PUFAs improved glucose transporter 4 expression, basal glucose uptake without insulin, and the AMP-activated protein kinase pathway. Of note, the long-chain PUFAs obstructed the effects of PA on the activation of extracellular-signal-regulated kinase and protein kinase C-θ as well as nuclear factor-κB (NF-κB) and activator protein-1. The inhibitory effect of AA but not of DHA and EPA on PA-induced inflammation and impaired insulin action was cancelled in C2C12 myotubes transfected with a constitutively active mutant IκB kinase-β plasmid. These data suggest that long-chain PUFAs may be useful in the management of PA-induced inflammation and insulin resistance in myotubes. In addition to the NF-κB pathway, other mechanisms are involved in the health benefits of DHA and EPA in PA-treated myotubes.
肌肉内脂质积累会引发炎症，这与骨骼肌中胰岛素作用受损相关，而骨骼肌是身体摄取葡萄糖的重要器官。在本研究中，我们探究了二十二碳六烯酸（DHA）、二十碳五烯酸（EPA）、花生四烯酸（AA）和长链多不饱和脂肪酸（PUFAs）对棕榈酸（PA）诱导的C2C12肌管炎症反应和胰岛素抵抗的影响。这三种受试长链多不饱和脂肪酸抑制了PA处理的肌管中促炎细胞因子白细胞介素-6和肿瘤坏死因子-α的mRNA表达。此外，长链多不饱和脂肪酸的添加降低了PA诱导的胰岛素抵抗，磷酸化AKT和葡萄糖摄取增加证明了这一点。在PA处理的肌管中，长链多不饱和脂肪酸改善了葡萄糖转运蛋白4的表达、无胰岛素时的基础葡萄糖摄取以及AMP激活的蛋白激酶途径。值得注意的是，长链多不饱和脂肪酸阻碍了PA对细胞外信号调节激酶和蛋白激酶C-θ以及核因子-κB（NF-κB）和激活蛋白-1激活的影响。在转染了组成型活性突变体IκB激酶-β质粒的C2C12肌管中，AA对PA诱导的炎症和胰岛素作用受损的抑制作用被消除，而DHA和EPA则没有。这些数据表明，长链多不饱和脂肪酸可能有助于管理PA诱导的肌管炎症和胰岛素抵抗。除了NF-κB途径外，其他机制也参与了DHA和EPA对PA处理的肌管的健康益处。
