Vitamin D Deficiency Attenuates Acute Alcohol-Induced Hepatic Lipid Accumulation in Mice.

Abstract

Vitamin D deficiency has been frequently reported in chronic liver disease. However, its influence on hepatic lipid accumulation in alcoholic liver disease remains unclear. The present study investigated the effects of vitamin D deficiency on acute alcohol-induced hepatic lipid metabolism in mice. Mice were fed with vitamin D deficient diet, in which vitamin D was depleted for 12 weeks to establish an animal model of vitamin D deficiency. Some mice were administered a single gavage of alcohol (4 g/kg bodyweight) before they were euthanized. Results show that feeding mice with vitamin D deficient diet did not induce hepatic lipid accumulation. In contrast, vitamin D deficiency markedly reduced alcohol-induced triacylglycerol (TAG) content and prevented hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated alcohol-induced sterol-regulated element-binding protein (SREBP)-1c activation, which regulates genes for hepatic fatty acid (FA) and TAG synthesis, and the expression of its target genes fatty acid synthase (Fasn) and acetyl-coenzyme- A carboxylase (Acc). In addition, vitamin D deficiency alleviated alcohol-induced downregulation of hepatic nuclear peroxisome proliferator-activated receptor (PPAR)α, which governs FA transport and β-oxidation, and the expression of Carnitine palmitoyltransferase (Cpt)-1α, cytochrome P450, family 4, subfamily a, polypeptide (Cyp4a)10, and Cyp4a14, which are key enzymes for hepatic fatty acids β-oxidation and ω-oxidation. Taken together, these results suggest that vitamin D deficiency is not a direct risk factor for hepatic lipid accumulation. Vitamin D deficiency alleviates acute alcohol-induced hepatic lipid accumulation through inhibiting hepatic de novo fatty acid syntheses and promoting fatty acid β-oxidation and ω-oxidation.