Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan.
Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan.
J Nutr Biochem. 2015 May;26(5):521-31. doi: 10.1016/j.jnutbio.2014.12.007. Epub 2015 Feb 7.
Skeletal muscle is a major site of insulin action. Intramuscular lipid accumulation results in inflammation, which has a strong correlation with skeletal muscle insulin resistance (IR). The aim of this study was to explore the effects of linoleic acid, alpha-linolenic acid, and gamma-linolenic acid (GLA), 18-carbon polyunsaturated fatty acids (PUFAs), on palmitic acid (PA)-induced inflammatory responses and IR in C2C12 myotubes. Our data demonstrated that these three test 18-carbon PUFAs can inhibit PA-induced interleukin-6 and tumor necrosis factor-α messenger RNA (mRNA) expression and IR as evidenced by increases in phosphorylated AKT and the 160-kD AKT substrate, mRNA and plasma membrane protein expression of glucose transporter 4, and glucose uptake. Moreover, the 18-carbon PUFAs blocked the effects of PA on activation of mitogen-activated protein kinases (MAPKs), protein kinase C-θ (PKC-θ), AMP-activated protein kinase (AMPK) and nuclear factor-κB (NF-κB). Of note, supplementation with GLA-rich borage oil decreased proinflammatory cytokine production and hindered the activation of MAPKs, PKC-θ and NF-κB in the skeletal muscles of diabetic mice. The 18-carbon PUFAs did not reverse PA-induced inflammation or IR in C2C12 myotubes transfected with a constitutively active mutant IκB kinase-β plasmid, which suggests the importance of the inhibition of NF-κB activation by the 18-carbon PUFAs. Moreover, blockade of AMPK activation by short hairpin RNA annulled the inhibitory effects of the 18-carbon PUFAs on PA-induced IR but not inflammation. Our findings suggest that the 18-carbon PUFAs may be useful in the management of PA-induced inflammation and IR in myotubes.
骨骼肌是胰岛素作用的主要部位。肌肉内脂质的积累会导致炎症，而炎症与骨骼肌胰岛素抵抗（IR）有很强的相关性。本研究旨在探讨亚油酸、α-亚麻酸和γ-亚麻酸（GLA），18 碳多不饱和脂肪酸（PUFA）对棕榈酸（PA）诱导的 C2C12 肌管炎症反应和 IR 的影响。我们的数据表明，这三种 18 碳 PUFAs 可以抑制 PA 诱导的白细胞介素-6 和肿瘤坏死因子-α信使 RNA（mRNA）表达和 IR，表现为磷酸化 AKT 和 160kD AKT 底物增加，葡萄糖转运体 4 的 mRNA 和质膜蛋白表达增加，以及葡萄糖摄取增加。此外，18 碳 PUFAs 阻断了 PA 对丝裂原激活蛋白激酶（MAPKs）、蛋白激酶 C-θ（PKC-θ）、AMP 激活蛋白激酶（AMPK）和核因子-κB（NF-κB）的激活作用。值得注意的是，富含 GLA 的琉璃苣油补充剂可减少促炎细胞因子的产生，并阻碍糖尿病小鼠骨骼肌中 MAPKs、PKC-θ 和 NF-κB 的激活。在转染组成性激活的 IκB 激酶-β质粒的 C2C12 肌管中，18 碳 PUFAs 并未逆转 PA 诱导的炎症或 IR，这表明 18 碳 PUFAs 抑制 NF-κB 激活的重要性。此外，短发夹 RNA 阻断 AMPK 激活可消除 18 碳 PUFAs 对 PA 诱导的 IR 的抑制作用，但对炎症没有影响。我们的研究结果表明，18 碳 PUFAs 可能有助于管理肌管中 PA 诱导的炎症和 IR。
