title: TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway.
abstract: High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway.
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Zhuqi
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Nana
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Suxin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: neifenmicui@163.com.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Cui
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: binghuodinghuo@163.com.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology*; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*
chemical_list: D016328:NF-kappa B; D010168:Palmitates; D047990:TNF Receptor-Associated Factor 1
keywords: Inflammation; Insulin resistance; NF-κB; TRAF1; Type 2 diabetes