Mitochondrial ACSS1-K-635 acetylation mimic knock-in mice exhibit altered lipid metabolism, hepatic cell senescence, and acute non-alcoholic fatty liver [1stSet_analysis]
We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine 635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate, and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis – consistent with nonalcoholic fatty liver disease (NAFLD). RNAseq analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Overall design: Fasted and fed C57BL/6J WT and ACSS1K635Q mice were studied in the context of non-alcoholic fatty liver disease. The liver tissue was collected and prepared for RNAseq as well as for Western blotting and qPCR analysis.