Nonalcoholic fatty liver disease (NAFLD) is a common liver disease, associated with insulin resistance. Betaine treatment would prevent or treat NAFLD in mice. Betaine reduces fasting glucose, insulin, triglycerides, and hepatic fat in mice submitted to a moderate high-fat diet (MHF). Betaine significantly improved insulin resistance and hepatic steatosis. Betaine treatment reversed the inhibition of hepatic insulin signaling in mHF and in insulin-resistant HepG2 cells, including normalization of insulin receptor substrate 1 (IRS1) phosphorylation and of signaling pathways for gluconeogenesis and glycogen synthesis. We can conclude that betaine treatment prevents and treats fatty liver in a moderate high-dietary-fat model of NAFL D in mice [70] .