Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver

Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD), although their relationship unclear. In transgenic zebrafish system with chronic systemic overexpression of human IL6 (IL6-OE) we show that inflammation can cause intra-hepatic accumulation triglycerides. Transcriptomics and proteomics analysis the IL6-OE liver revealed deregulation glycolysis/gluconeogenesis pathway, especially striking down regulation glycolytic enzyme aldolase b. Metabolomics by mass spectrometry showed hexose monophosphates derivatives, which act as precursors for triglyceride synthesis. Our results suggest IL6-driven repression glycolysis/gluconeogenesis, specifically b, may be novel mechanism fatty liver. This relevant NAFLD lean individuals, an emerging class prevalent more Asian Indian populations.