This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S. Articles by Lee, J. W. Search for Related Content PubMed PubMed Citation Articles by Lee, S. Articles by Lee, J. W.

Identification of a Functional Vitamin D Response Element in the Murine Insig-2 Promoter and Its Potential Role in the Differentiation of 3T3-L1 Preadipocytes

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine (D.-K.L., J.W.L.), Department of Molecular & Cellular Biology (S.L., J.W.L.), Baylor College of Medicine, Houston, Texas 77030; and Department of Life Science (E.C.), Pohang University of Science and Technology, Pohang 790-784, Korea

Address all correspondence and requests for reprints to: Jae W. Lee, Ph.D., Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Dept. Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030. E-mail: jwlee{at}bcm.tmc.edu.

Insulin-induced gene-1 (Insig-1) and its homolog Insig-2 encode closely related proteins of the endoplasmic reticulum that block proteolytic activation of sterol regulatory element binding proteins, membrane-bound transcription factors that activate synthesis of cholesterol and fatty acids in animal cells. These proteins also restrict lipogenesis in mature adipocytes and block differentiation of preadipocytes. Herein, we identified a novel 1,25-dihydroxyvitamin D3 [1,25-(OH)₂D₃] response element in the promoter region of Insig-2 gene, which specifically binds to the heterodimer of retinoid X receptor and vitamin D receptor (VDR) and directs VDR-mediated transcriptional activation in a 1,25-(OH)₂D₃-dependent manner. Interestingly, 1,25-(OH)₂D₃ is known to directly suppress the expression of peroxisome proliferator-activated receptor 2 protein and inhibits adipocyte differentiation of 3T3-L1 preadipocytes and murine bone marrow stromal cells. Consistent with an idea that the antiadipogenic action of 1,25-(OH)₂D₃ may also involve up-regulation of Insig-2, we found that 1,25-(OH)₂D₃ transiently but strongly induces Insig-2 expression in 3T3-L1 cells. This novel regulatory circuit may also play important roles in other lipogenic cell types that express VDR, and collectively our results suggest an intriguing, new linkage between 1,25-(OH)₂D₃ and lipogenesis.

NURSA Molecule Pages Link:

Nuclear Receptors:   RARα  |  PPARγ  |  LXRα  |  FXRα  |  VDR  |  RXRα

Ligands:   T0901317  |  Calcitriol  |  Dexamethasone  |  9-cis-Retinoic acid  |  Rosiglitazone

This article has been cited by other articles:

				E. Liu, J. B. Meigs, A. G. Pittas, N. M. McKeown, C. D. Economos, S. L. Booth, and P. F. Jacques Plasma 25-Hydroxyvitamin D Is Associated with Markers of the Insulin Resistant Phenotype in Nondiabetic Adults J. Nutr., February 1, 2009; 139(2): 329 - 334. [Abstract] [Full Text] [PDF]

				E. De Marinis, C. Martini, A. Trentalance, and V. Pallottini Sex differences in hepatic regulation of cholesterol homeostasis J. Endocrinol., September 1, 2008; 198(3): 635 - 643. [Abstract] [Full Text] [PDF]

				T. Reinehr, A. Hinney, T. T. Nguyen, and J. Hebebrand Evidence of an Influence of a Polymorphism Near the INSIG2 on Weight Loss During a Lifestyle Intervention in Obese Children and Adolescents Diabetes, March 1, 2008; 57(3): 623 - 626. [Abstract] [Full Text] [PDF]

				M. L. Hubbert, Y. Zhang, F. Y. Lee, and P. A. Edwards Regulation of Hepatic Insig-2 by the Farnesoid X Receptor Mol. Endocrinol., June 1, 2007; 21(6): 1359 - 1369. [Abstract] [Full Text] [PDF]

				T. Ohnesorg, B. Keller, M. H. de Angelis, and J. Adamski Transcriptional regulation of human and murine 17{beta}-hydroxysteroid dehydrogenase type-7 confers its participation in cholesterol biosynthesis. J. Mol. Endocrinol., August 1, 2006; 37(1): 185 - 197. [Abstract] [Full Text] [PDF]

				J. Kong and Y. C. Li Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E916 - E924. [Abstract] [Full Text] [PDF]

				J. M. Blumberg, I. Tzameli, I. Astapova, F. S. Lam, J. S. Flier, and A. N. Hollenberg Complex Role of the Vitamin D Receptor and Its Ligand in Adipogenesis in 3T3-L1 Cells J. Biol. Chem., April 21, 2006; 281(16): 11205 - 11213. [Abstract] [Full Text] [PDF]