SIRT3 and fatty liver disease: Zhang et al reported that caffeine improved hepatic steatosis partly by activation of SIRT3/AMPK pathway, and SIRT3 silencing decreased the AMPK phosphorylation in the liver.49 Another study indicated that SIRT3 could reduce lipid accumulation through AMPK activation in human hepatic cells, and further proved that the activity of SIRT3 deacetylase was required for SIRT3 to activate AMPK.48 On the contrary, accumulating evidence suggested that AMPK could regulate SIRT3.