Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals,(27) In addition, NAD+ homeostasis is emerging as a key player in the pathogenesis of NAFLD and is tightly linked to the SIRT1/5'-AMP-activated protein kinase (AMPK) pathway.(28) SIRT1 is known to be involved in gluconeogenesis and fatty acid oxidation in the liver. Here, SIRT1 is linked to metabolic dysfunction-associated steatotic liver disease.