Vitamin D attenuates high fat diet–induced hepatic steatosis in rats by modulating lipid metabolism

Abstract

Vitamin D has been reported to be reversely associated with type 2 diabetes and metabolic syndrome and is involved in modulation of lipid metabolism. The purpose of the present study was to determine whether 1,25-dihydroxyvitamin D(3) (1,25(OH)(2) D(3) ) has a protective effect on high fat diet (HFD)-induced hepatic steatosis in rats and to elucidate its underlying molecular mechanisms. Male Sprague-Dawley (SD) rats were fed with normal fat diet, HFD or HFD with intraperitoneal injection of 1, 2.5 and 5 μg/kg 1,25(OH)(2) D(3) , respectively, each 2 days for 8 weeks. Serum lipid profile and liver triglyceride were determined. Hepatic histology was examined by haematoxylin/eosin (H&E) and Oil Red O stainings. Hepatic gene expression involved in lipogenesis and lipid oxidation was analysed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The administration of 1,25(OH)(2) D(3) prevented HFD-induced body weight gain and reduced liver weight. 1,25(OH)(2) D(3) attenuated hepatic steatosis in a dose-dependent manner along with improved serum lipid profile. Furthermore, 1,25(OH)(2) D(3) downregulated mRNA expression of sterol regulatory element binding protein-1c (SREBP-1c) and its target genes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) involved in lipogenesis. Peroxisome proliferator-activated receptor α (PPARα) and its target gene carnitine palmitoyltransferase-1 (CPT-1) involved in hepatic fatty acid (FA) oxidation were upregulated by 1,25(OH)(2) D(3) . These results suggest that the preventing effect of 1,25(OH)(2) D(3) against HFD-induced hepatic steatosis is related to the inhibition of lipogenesis and the promotion of FA oxidation in rat liver.