gp130 Activates Mitochondrial Dynamics for Hepatocyte Survival in a Model of Steatohepatitis

Abstract

Obesity is the main cause of metabolic complications. Fatty liver infiltration is a companion of obesity. NAFLD is associated with impaired energy metabolism with an excess of nutrients. Mitochondrial dynamics are important for the regulation of energy balance, which regulates mitochondrial function, apoptosis, and mitophagy. The aim of this study was to investigate the effect of gp130 on the components of mitochondrial dynamics in a cellular model of steatohepatitis. Addition of IL-6/gp130 contributed to an increase in the percentage of live cells and a decrease in the percentage of dead and apoptotic cells. Addition of IL-6/gp130 increased the expression of NF-kB1 gene and mitochondrial dynamics markers (MFN2 and TFAM) in HepG2 with tBHP/Oleic. Addition of IL-6 or gp130 reduced the expression of cytoprotector genes (HSF1 and HSP70) in HepG2 cell cultures with tBHP/Oleic. Increased mitochondrial dynamics gene activity protected against HepG2 cell death in the steatohepatitis model. Trans-signaling resulted in increased TFAM and MAPLC3B, and decreased DNM1L gene expression in HepG2 with tBHP/Oleic.

Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease—Oxidative Stress and Inflammation Relevance

“…The involvement of interleukin 6 (IL-6) in the pathogenesis of NAFLD is usually seen as a possible therapeutic target, as it participates in numerous cellular events. In this case, the blockage of the IL-6 signal leads to the activation of the mitochondrial fusion gen [ 119 ]. IL-6 is implicated in inflammation, redox processes, and the promotion of IR.…”