title: KPNβ1 promotes palmitate-induced insulin resistance via NF-κB signaling in hepatocytes.
abstract: 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 β1 (KPNβ1) in hepatic insulin resistance and the underlying mechanisms using high-fat diet (HFD) fed mice and palmitate (PA)-stimulated hepatocytes (HepG2). KPNβ1 expression is increased in the HFD fed mice liver. PA upregulated KPNβ1 expression in HepG2 cells in a time-dependent manner. PA also increased pro-inflammatory cytokines expression, including tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β). KPNβ1 knockdown reversed PA-induced pro-inflammatory cytokines expression and insulin-stimulated glucose uptake in HepG2 cells. In addition, KPNβ1 knockdown reduced intracellular lipid accumulation. Mechanistically, KPNβ1 transports nuclear factor kB (NF-κB) p65 from the cytoplasm to the nucleus to increase pro-inflammatory genes expression. In summary, KPNβ1 acts as a positive regulator in the NF-κB pathway to enhance palmitate-induced inflammation response and insulin resistance in HepG2 cells.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Suxin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Zhuqi
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China. cuishiwei2009@163.com.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Cui
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000502:physiology*; D010168:Palmitates; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D028961:beta Karyopherins
chemical_list: D007328:Insulin; C094999:Kpnb1 protein, mouse; D009687:Nuclear Proteins; D010168:Palmitates; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D028961:beta Karyopherins
keywords: Inflammation; Insulin resistance; KPNβ1; NF-κB