However, Vatner et al., in a mouse model of high-fat diet (HFD) induced NAFLD, subsequently disavowed this hypothesis, proposing the existence of different synergic alternative mechanisms responsible for the concomitant increase in DNL and gluconeogenesis in insulin-resistant liver tissue, including the hyperinsulinemia, insulin-independent re-esterification of adipose tissue-derived FFAs as well as the enhanced generation of acetyl CoA via pyruvate carboxylase (PC) activation [19,20]. Here, INS is linked to metabolic dysfunction-associated steatotic liver disease.