Vitamin D and adipogenesis: new molecular insights
Richard J Wood,
Corresponding Author
Richard J Wood
Mineral Bioavailability Laboratory at Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
RJ Wood, Mineral Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. E-mail: [email protected], Phone: +1-617-556-3192, Fax: +1-617-556-3344Search for more papers by this authorRichard J Wood,
Corresponding Author
Richard J Wood
Mineral Bioavailability Laboratory at Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
RJ Wood, Mineral Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. E-mail: [email protected], Phone: +1-617-556-3192, Fax: +1-617-556-3344Search for more papers by this authorAbstract
The focus of the current review is to highlight some new insights into the molecular mechanism by which vitamin D, a potentially nutritionally modulated factor, influences adipogenesis. Recent studies, predominantly using the mouse 3T3-L1 pre-adipocyte cell culture model, have shown that the role of vitamin D in inhibiting adipogenesis is mediated at the molecular level through a vitamin D receptor (VDR)-dependent inhibition of CCAAT enhancer binding protein-alpha (C/EBPα) and peroxisome proliferator-activated receptor-gamma (PPARγ) expression and a decrease in PPARγ transactivating activity in the pre-adipocyte. The latter action may reflect a vitamin D-induced decrease in endogenous PPARγ ligand availability and a competition between VDR and PPARγ for a limiting amount of retinoid X receptor (RXR), a common heterodimeric binding partner of both nuclear receptors.
REFERENCES
- 1 Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 2006; 7: 885–896.
- 2 Tzameli I, Fang H, Ollero M, et al. Regulated production of a peroxisome proliferator-activated receptor-gamma ligand during an early phase of adipocyte differentiation in 3T3-L1 adipocytes. J Biol Chem 2004; 279: 36093–36102.
- 3 Martini LA, Wood RJ. Vitamin D status and the metabolic syndrome. Nutr Rev 2006; 64: 479–486.
- 4 Florez H, Martinez R, Chacra W, Strickman-Stein N, Levis S. Outdoor exercise reduces the risk of hypovitaminosis D in the obese. J Steroid Biochem Mol Biol 2007; 103: 679–681.
- 5 Hahn S, Haselhorst U, Tan S, et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2006; 114: 577–583.
- 6 Hypponen E, Power C. Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Diabetes Care 2006; 29: 2244–2246.
- 7 Feldman D, Pike J, Glorieux F, eds. Vitamin D. San Diego, CA: Academic Press; 2004.
- 8 Sutton AL, MacDonald PN. Vitamin D: more than a “bone-a-fide” hormone. Mol Endocrinol 2003; 17: 777–791.
- 9 Chen TC, Chimeh F, Lu Z, et al. Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophys 2007; 460: 213–217.
- 10 Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006; 116: 2062–2072.
- 11 Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr 2005; 135: 310–316.
- 12 Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol 2006; 92: 60–64.
- 13 Liu PT, Krutzik SR, Modlin RL. Therapeutic implications of the TLR and VDR partnership. Trends Mol Med 2007; 13: 117–124.
- 14 Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis 2005; 20: 187–192.
- 15 Blumberg JM, Tzameli I, Astapova I, Lam FS, Flier JS, Hollenberg AN. Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells. J Biol Chem 2006; 281: 11205–11213.
- 16 Kong J, Li YC. Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am J Physiol Endocrinol Metab 2006; 290: E916–924.
- 17 Rangwala SM, Lazar MA. Transcriptional control of adipogenesis. Annu Rev Nutr 2000; 20: 535–559.
- 18 Kim JB, Wright HM, Wright M, Spiegelman BM. ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci USA 1998; 95: 4333– 4337.
- 19 Hamm JK, Park BH, Farmer SR. A role for C/EBPbeta in regulating peroxisome proliferator-activated receptor gamma activity during adipogenesis in 3T3-L1 preadipocytes. J Biol Chem 2001; 276: 18464–18471.
- 20 Ishida Y, Taniguchi H, Baba S. Possible involvement of 1 alpha,25-dihydroxyvitamin D3 in proliferation and differentiation of 3T3-L1 cells. Biochem Biophys Res Commun 1988; 151: 1122–1127.
- 21 Sato M, Hiragun A. Demonstration of 1 alpha,25-dihydroxyvitamin D3 receptor-like molecule in ST 13 and 3T3 L1 preadipocytes and its inhibitory effects on preadipocyte differentiation. J Cell Physiol 1988; 135: 545–550.
- 22 Kamei Y, Kawada T, Kazuki R, Ono T, Kato S, Sugimoto E. Vitamin D receptor gene expression is up-regulated by 1,25-dihydroxyvitamin D3 in 3T3-L1 preadipocytes. Biochem Biophys Res Commun 1993; 193: 948–955.
- 23 Hida Y, Kawada T, Kayahashi S, Ishihara T, Fushiki T. Counteraction of retinoic acid and 1,25-dihydroxyvitamin D3 on up-regulation of adipocyte differentiation with PPARgamma ligand, an antidiabetic thiazolidinedione, in 3T3-L1 cells. Life Sci 1998; 62: PL205–211.
- 24 Elberg G, Gimble JM, Tsai SY. Modulation of the murine peroxisome proliferator-activated receptor gamma 2 promoter activity by CCAAT/enhancer-binding proteins. J Biol Chem 2000; 275: 27815–27822.
- 25 Rochford JJ, Semple RK, Laudes M, et al. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis. Mol Cell Biol 2004; 24: 9863–9872.
- 26 Rosen ED, Hsu C-H, Wang X, et al. C/EBPalpha induces adipogenesis through PPARgamma : a unified pathway. Genes Dev 2002; 16: 22–26.
