A role of 1,25(OH)2D3 supplementation in rats with nonalcoholic steatohepatitis induced by choline-deficient diet

- 1,25(OH)2D3 protects against choline deficiency-induced nonalcoholic steatohepatitis.
- 1,25(OH)2D3 restrains hepatic accumulation of free fatty acid.
- 1,25(OH)2D3 supplementation attenuates lipid peroxidation in the liver.
- 1,25(OH)2D3 supplementation restrains the production of CK18-M30 in the liver.
- Higher doses of 1,25(OH)2D3 may lead to certain adverse effects.

Background and aimsIt has been reported that 1,25(OH)2D3 (1,25-VD3) ameliorates the progression of nonalcoholic steatohepatitis (NASH). However, it is unclear whether 1,25-VD3 plays a role in NASH induced by a choline-deficient (CD) diet. In this study, we investigated the roles of 1,25-VD3 in the development and progression of NASH in rats induced by a CD diet.Methods and resultsWistar rats with NASH induced by a CD diet were subjected to intraperitoneal injections of 1, 5, or 10 μg/kg of 1,25-VD3 twice weekly for 12 weeks. The administration of 1,25-VD3 decreased free fatty acids (FFAs), triglycerides (TGs), thiobarbituric acid-reactive substances (TBARS), the number of apoptotic cells, and the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the liver, and it improved liver histology, but it did not change the total antioxidant capacity (TAOC) in the liver. Interestingly, the level of CK18-M30 was decreased in the liver of model animals. Treatment with 1,25-VD3 may restrain the downregulation of CK18-M30 in the liver and its release into the bloodstream, thus decreasing the level of serum CK18-M30. 1,25-VD3 supplementation elevated the serum level of 25(OH)D3 and the expression of VDR in the liver. The dose-effect relationship of 1,25-VD3 indicated that 1,25-VD3 slows down the development and progression of NASH induced by a CD diet, but higher doses of 1,25-VD3 may lead to adverse effects.ConclusionThe results suggest the presence of both antagonistic and adverse dose-dependent effects of the long-term supplementation of 1,25-VD3 on NASH induced by a CD diet.