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.

Lactoferrin Alleviates Acute Alcoholic Liver Injury by Improving Redox-Stress Response Capacity in Female C57BL/6J Mice

“…Thus, we first investigated whether similar regulatory mechanisms were involved in the acute ALI prevention in female mice. As reported by many studies, − our study also found that acute alcohol intake upregulated CYP2E1 protein expression and increased ALDH activity. However, neither LLf nor HLf affected the alcohol metabolism key enzymes including CYP2E1, ADH, and ALDH.…”

Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice

“…Indeed, there remains with debate concerning the role of vitamin D on lipid metabolism [54][55][56][57]. Of interest, our previous study found that vitamin D deficiency alleviates acute alcohol-induced hepatic lipid accumulation [58]. These results suggest that the effects of vitamin D deficiency on alcohol-induced hepatic lipid accumulation might correlate with the mode and time of alcohol exposure.…”

Salmon sperm DNA prevents acute liver injury by regulating alcohol‐induced steatosis and restores chronic hepatosis via alleviating inflammation and apoptosis

“…As reported previously, acute alcohol intoxication affected the circulating hepatic and systemic lipidome, which increased triglyceride (TG) levels and caused an obvious hepatic lipid accumulation (Hu et al, 2019). In the present study, we found that early intervention with salmon sperm DNA resulted in significant reductions in cholesterol and triglyceride levels in serum and liver to protect against alcoholic liver injury.…”

“…In contrast, treatment with salmon sperm DNA can decrease the protein level of PPARα. Furthermore, SREBP‐1c is the most important transcription factor regulating hepatic fatty acid and TG synthesis genes, as well as ACC, FAS, and SCD1 expression (Hu et al, 2019; Jeon & Carr, 2020). In the present study, the liver SREBP‐1c, Scd1, and Fas mRNA levels of the model group were significantly increased compared to those of the control group.…”