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

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.