A prerequisite or “first step” for NASH appears to be adipose tissue insulin resistance, providing the necessary “lipotoxic environment” that ensures ample substrate supply to the liver (i.e., high FFA flux) and compensatory hyperinsulinemia that stimulates excessive hepatic triglyceride synthesis and the formation of toxic saturated fatty acids. The gene discussed is INS; the disease is metabolic dysfunction-associated steatohepatitis.