The Study Of Spermidine Regulating Liver Lipid Metabolism

With the improvement of people's living standards,the incidence of metabolic diseases such as non-alcoholic fatty liver disease and obesity is increasing[1].Amp-dependent protein kinase,AMPK,is a key kinase for energy metabolism in the body.Studies have shown that many drugs target AMPK to treat metabolic diseases such as obesity[2].Spermine is a polyamine compound.Studies have shown that spermidine can promote longevity,and has strong anti-inflammatory and antioxidant effects,as well as anti-atherosclerosis[3,4].Based on the above studies,we hypothesized that whether spermidine is involved in lipid metabolism can further alleviate the symptoms of non-alcoholic fatty liver disease.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 pro-tein 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.