SHMT2 reduces fatty liver but is necessary for liver inflammation and fibrosis in mice

Non-alcoholic fatty liver disease is linked to disrupted serine metabolism. SHMT2 is a liver enzyme that is crucial for liver methylation and overall health. We developed a mouse strain with targeted SHMT2 knockout in hepatocytes and found that the absence of SHMT2 led to increased circulating serine and glycine levels, 1C deficiency, and depleted liver methylation potential. The study reveals the critical role of SHMT2 in maintaining hepatic 1C homeostasis and regulating the progression of non-alcoholic fatty liver disease. To investigate the metabolic function of SHMT2 in intact animals, we established a mouse model with liver-specific SHMT2 deletion We treated the animals with the AMLN diet that promotes diet-induced non-alcoholic fatty liver disease. We conducted a comparison of liver gene expression using RNA sequencing.