Calcium and vitamin D₃ combinations improve fatty liver disease through AMPK-independent mechanisms

Some research findings suggest that calcium plus vitamin D (VitD) might have a preventive effect on nonalcoholic fatty liver disease development. Moreover, contradictory evidence also exists regarding calcium and VitD deficient diets. This study aimed to evaluate the effect of four different dietary calcium and VitD₃ (cholecalciferol) levels on the development of high-fat, high-fructose (HFHFr) diet-induced nonalcoholic fatty liver disease and AMP-activated protein kinase (AMPK) phosphorylation.

Thirty male Wistar rats were fed with normal or HFHFr diet containing low calcium (0.2%) and VitD₃ (250 IU/kg) (LCD), normal calcium (0.5%) and VtD₃ (1000 IU/kg) (CN), high calcium (1.2%) and VitD₃ (4000 IU/kg) (HCD) or very high amount of calcium (2.4%) and VitD₃ (10,000 IU/kg) (VHCD). After 60 days, anthropometric, metabolic and hepatic parameters were evaluated. The effect of the experimental diets on liver AMPK phosphorylation was also investigated.

Rats fed on high calcium plus VitD₃ diets, especially VHCD, demonstrated lower adiposity, serum liver enzymes, hepatic lipid accumulation and steatosis. The LCD diet also decreased hepatic lipid content and fatty changes. No evidence indicating the involvement of AMPK in the observed associations was found (P value = 0.51).

The results showed high calcium plus VitD₃ intakes considerably prevent biochemical and hepatic changes induced by HFHFr diet, probably via an insulin and AMPK-independent pathway. A low intake of these two nutrients was also linked with a significant decrease in HFHFr diet-induced hepatic steatosis.