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

Seunghee Lee, Dong Kee Lee, Eunho Choi, Jae Lee

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 1α,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)2D 3-dependent manner. Interestingly, 1,25-(OH)2D3 is known to directly suppress the expression of peroxisome proliferator- activated receptor γ2 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)2D 3 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.

Original languageEnglish (US)
Pages (from-to)399-408
Number of pages10
JournalMolecular Endocrinology
Volume19
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

Vitamin D Response Element
Calcitriol Receptors
Lipogenesis
Adipocytes
Sterol Regulatory Element Binding Proteins
3T3-L1 Cells
Retinoid X Receptors
Peroxisome Proliferator-Activated Receptors
Proteins
Calcitriol
Response Elements
Mesenchymal Stromal Cells
Genetic Promoter Regions
Endoplasmic Reticulum
Transcriptional Activation
Genes
Transcription Factors
Up-Regulation
Fatty Acids
Cholesterol

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Lee, Seunghee; Lee, Dong Kee; Choi, Eunho; Lee, Jae.

In: Molecular Endocrinology, Vol. 19, No. 2, 02.2005, p. 399-408.

Research output: Contribution to journalArticle

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