title: 18-carbon polyunsaturated fatty acids ameliorate palmitate-induced inflammation and insulin resistance in mouse C2C12 myotubes.
abstract: 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.
authors: Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan.
authors: Pei-Yin
authors: PY
authors: Chen
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan.
authors: John
authors: J
authors: Wang
authors: Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan; Department of Dietitian, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Yi-Chin
authors: YC
authors: Lin
authors: Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan; Department of Dietitian, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Chien-Chun
authors: CC
authors: Li
authors: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors: Chia-Wen
authors: CW
authors: Tsai
authors: Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan; Department of Dietitian, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Te-Chung
authors: TC
authors: Liu
authors: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors: Haw-Wen
authors: HW
authors: Chen
authors: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors: Chin-Shiu
authors: CS
authors: Huang
authors: Department of Nutrition, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. Electronic address: cklii@mail.cmu.edu.tw.
authors: Chong-Kuei
authors: CK
authors: Lii
authors: Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 40203, Taiwan; Department of Dietitian, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: kaililiu@csmu.eud.tw.
authors: Kai-Li
authors: KL
authors: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D019308:Palmitic Acid / Q000633:toxicity*
chemical_list: D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D019308:Palmitic Acid
keywords: 18-Carbon polyunsaturated fatty acids (18-Carbon PUFAs); AMP-activated protein kinase (AMPK); Inflammation; Insulin resistance (IR); Nuclear factor-κB (NF-κB)