| Purpose: Metformin is one of the most popular drugs tested against nonalcoholic fatty liver
disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D3
cosupplementation will intensify the effect of metformin on the prevention of high-fat, highfructose
(HFFr) diet-induced hepatic steatosis.
Methods: 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 D3) or high amount of calcium and
vitamin D3 (2.4% calcium and 10000 IU/kg vitamin D3) (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.
Results: 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.
Conclusion: 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. |