Clarification of the mechanism by which the impairment of intra-hepatic cellular network caused hepatic insulin resistance in mice.

We examined the effect of spironolactone on glucose and lipid metabolism in a mouse model with diet-induced diabetes and non-alcoholic fatty liver disease (NAFLD). C57BL/6 mice were fed control diet, 60% fat diet with 30% fructose water (HFFD), or HFFD with spironolactone for 8 weeks. HFFD mice demonstrated apparent phenotypes of metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and fatty liver. Administration of spironolactone effectively ameliorated these phenotypes. These results indicate that inhibition of MR might be a beneficial therapeutic approach for diet-induced phenotypes of metabolic syndrome and fatty liver.