Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK.

In this study, treatment of high-fat diet-induced obesity (DIO) C57BL/6J mice with spermidine decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular and serum triglyceride and total cholesterol concentrations. Moreover, spermidine treatment improved glucose tolerance and insulin sensitivity in DIO mice. The mechanism studies indicated that spermidine indeed increased the phosphorylation of hepatic AMP-activated protein kinase (AMPK), and inhibited the expression of lipogenic genes in vivo and in vitro. Moreover, these spermidine-mediated molecular effects were also abolished by compound C, an inhibitor of AMPK, in primary hepatocytes. In summary, spermidine protected against DIO-induced hepatosteatosis by decreasing lipogenic genes expression through an AMPK-mediated mechanism.