FASN and hyperinsulinism: It phosphorylates upstream stimulatory factor 1 (USF1) and then upregulate fatty acid synthase (FASN), which promotes de novo lipogenesis (DNL) in liver and aggravates hepatic fat deposition.76 The altered membrane potential of hepatocytes after adipose deposition causes γ-aminobutyric acid (GABA) release and inhibits the vagus nerve, which is also involved in hyperinsulinemia.77 In turn, hyperinsulinemia due to IR in the liver and other target tissues can promote the production of liver fat, resulting in a vicious cycle.