title: Regulation of Adipogenesis and Key Adipogenic Gene Expression by 1, 25-Dihydroxyvitamin D in 3T3-L1 Cells.
abstract: The functions of 1, 25-dihydroxyvitamin D (1, 25-(OH)2D3) in regulating adipogenesis, adipocyte differentiation and key adipogenic gene expression were studied in 3T3-L1 preadipocytes. Five concentrations (0.01, 0.1, 1, 10, 100 nM) of 1, 25-(OH)2D3 were studied and lipid accumulation measured by Oil Red O staining and expression of adipogenic genes quantified using quantitative real-time PCR. Adipogenic responses to 1, 25-(OH)2D3 were determined on 6, and 12 h, and days 1-10 after induction of adipogenesis by a hormonal cocktail with or without 1, 25-(OH)2D3. In response to 1, 25-(OH)2D3 (1, 10, and 100 nM), lipid accumulation and the expression of PPARγ, C/EBPα, FABP4 and SCD-1 were inhibited through day 10, and vitamin D receptor expression was inhibited in the early time points. The greatest inhibitory effect was upon expression of FABP4. Expression of SREBP-1c was only affected on day 2. The lowest concentrations of 1, 25-(OH)2D3 tested did not affect adipocyte differentiation or adipogenic gene expression. The C/EBPα promoter activity response to 1, 25-(OH)2D3 was also tested, with no effect detected. These results indicate that 1, 25-(OH)2D3 inhibited adipogenesis via suppressing adipogenic-specific genes, and is invoked either during PPARγ activation or immediately up-stream thereof. Gene expression down-stream of PPARγ especially FABP4 was strongly inhibited, and we suggest that the role of 1, 25-(OH)2D3 in regulating adipogenesis will be informed by further studies of adipogenic-specific gene promoter activity.
authors.affiliation: Department of Animal and Veterinary Sciences, University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Shuhan
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Animal and Veterinary Sciences, University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Doumit
authors.affiliation: Department of Animal and Veterinary Sciences, University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Hill
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase