SIRT1 and metabolic dysfunction-associated steatohepatitis: We have previously demonstrated that L-Leucine, which is an allosteric Sirt1 activator, synergizes with low doses of metformin, an AMPK activator, and sildenafil, which is a well-known PDE 5 inhibitor, to modulate hepatic lipid metabolism and reverse NASH in preclinical mouse models [8,9,10,11].