| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 16, 2004
Accepted on October 25, 2004
Div. Diabetes, Endocrinology & Metabolism, Dept. Medicine, Dept. Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030; Dept. Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea
* To whom correspondence should be addressed. E-mail: jwlee{at}bcm.tmc.edu.
Insulin induced gene-1 (Insig-1) and its homologue 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 1alpha,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 (PPAR) 
2 protein and inhibits adipocyte differentiation of 3T3-L1 preadipocytes and murine bone marrow stromal cells. Consistent with an idea that the anti-adipogenic 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:
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
