KPNß1 promotes palmitate-induced insulin resistance via NF-?B signaling in hepatocytes

• Autores: Suxin Wang, Yun Zhao, Nana Xia, Wanlu Zhang, Zhuqi Tang, Cuifang Wang
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 71, Nº. 4, 2015, págs. 763-772
• Idioma: inglés
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• Resumen

  • It has been intensively studied that inflammation contributes to the insulin resistance development in obesity-induced type 2 diabetes mellitus (T2DM). In this study, we assessed the effect of karyopherin ß1 (KPNß1) in hepatic insulin resistance and the underlying mechanisms using high-fat diet (HFD) fed mice and palmitate (PA)-stimulated hepatocytes (HepG2). KPNß1 expression is increased in the HFD fed mice liver. PA upregulated KPNß1 expression in HepG2 cells in a time-dependent manner. PA also increased pro-inflammatory cytokines expression, including tumor necrosis factor a (TNF-a), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß). KPNß1 knockdown reversed PA-induced pro-inflammatory cytokines expression and insulin-stimulated glucose uptake in HepG2 cells. In addition, KPNß1 knockdown reduced intracellular lipid accumulation. Mechanistically, KPNß1 transports nuclear factor kB (NF-?B) p65 from the cytoplasm to the nucleus to increase pro-inflammatory genes expression. In summary, KPNß1 acts as a positive regulator in the NF-?B pathway to enhance palmitate-induced inflammation response and insulin resistance in HepG2 cells.