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

Eur J Clin Invest. 2012 Nov;42(11):1189-96. doi: 10.1111/j.1365-2362.2012.02706.x. Epub 2012 Sep 8.


Background: 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.

Materials and methods: 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).

Results: 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) .

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Calcitriol / pharmacology*
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Diet, High-Fat / adverse effects*
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Gene Expression
  • Lipid Metabolism / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Organ Size
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / genetics
  • Triglycerides / metabolism


  • PPAR alpha
  • RNA, Messenger
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Carnitine O-Palmitoyltransferase
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase
  • Calcitriol