The Eeffect of Metformin Combined with Calcium-Vitamin D Against Diet-Induced Nonalcoholic Fatty Liver Disease.

Metformin is one of the most popular drugs tested against nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D cosupplementation will intensify the effect of metformin on the prevention of high-fat, high-fructose (HFFr) diet-induced hepatic steatosis. Male wistar rats (210±16 g) were assigned into the following seven groups: a Control group to receive a standard chow and six HFFr-fed groups to receive diets containing either normal (0.5% calcium and 1000 IU/kg vitamin D) or high amount of calcium and vitamin D (2.4% calcium and 10000 IU/kg vitamin D) (CaD), in combination with gastric gavage administration of either saline or 25 or 200 mg/kg body weight/day metformin. After 60 days, rats were assessed with respect to their anthropometric, metabolic and hepatic parameters, as well as their hepatic AMP-activated protein kinase (AMPK) phosphorylation. Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation. In addition, slightly (and non-significantly) better effects of the combination in ameliorating steatosis and hepatic cholesterol content were observed. Taken together, our results suggest that metformin and CaD could protect against the onset of HFFr diet-induced NAFLD in an insulin and AMPK-independent manner, without any marked additional benefits of their combination.