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: Suxin Wang, Yun Zhao, Nana Xia, Wanlu Zhang, Zhuqi Tang, Cuifang Wang, Xiaohui Zhu, Shiwei Cui
• Journal: Journal of physiology and biochemistry (J Physiol Biochem) Vol. 71 Issue 4 Pg. 763-72 (Dec 2015) ISSN: 1877-8755 [Electronic] Spain
• PMID: 26452501 (Publication Type: Journal Article)

Chemical References

• Insulin
• Kpnb1 protein, mouse
• Nuclear Proteins
• Palmitates
• Rela protein, mouse
• Transcription Factor RelA
• beta Karyopherins

Topics

• Active Transport, Cell Nucleus
• Animals
• Hep G2 Cells
• Hepatocytes (metabolism)
• Humans
• Insulin (physiology)
• Insulin Resistance
• Liver (metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Nuclear Proteins (physiology)
• Palmitates
• Signal Transduction
• Transcription Factor RelA (metabolism)
• beta Karyopherins