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Regulatory sequence elements of mouse GLUT4 gene expression in adipose tissues
Shinji Miura1, Nobuyo Tsunoda, Shinobu Ikeda
1Division of Clinical Nutrition, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Biochemical and Biophysical Research Communications
|November 26, 2003
Summary
Researchers identified key regulatory elements in the GLUT4 gene. These elements control glucose transporter type 4 (GLUT4) expression in adipose tissue and its response to high-fat diets, impacting insulin resistance.
Area of Science:
- Molecular Biology
- Metabolic Regulation
- Genetics
Background:
- Adipose tissue GLUT4 (glucose transporter type 4) is crucial for whole-body insulin sensitivity.
- Insulin resistance is linked to reduced GLUT4 expression in white adipose tissue, particularly under high-fat diets.
- Previous research localized adipose tissue-specific elements (ASE) and high-fat-responsive elements (HFRE) within the murine GLUT4 gene's 5'-flanking region.
Purpose of the Study:
- To further characterize the regulatory elements controlling GLUT4 gene expression in adipose tissue.
- To pinpoint the precise locations of ASE and HFRE within the GLUT4 gene.
- To investigate the distinct roles of these elements in response to dietary factors.
Main Methods:
- Generation and analysis of transgenic mice carrying GLUT4 minigenes with varying lengths of the 5'-flanking region (-701, -551, -506 bp).
- Quantification of GLUT4 minigene mRNA expression in adipose tissues of transgenic mice under normal and high-fat diet conditions.
- Identification of nuclear DNA-binding proteins interacting with specific GLUT4 gene sequences using electrophoretic mobility shift assays (EMSA).
Main Results:
- A critical adipose tissue-specific element (ASE) was localized to a 45 bp region between bases -551 and -506 of the GLUT4 gene.
- An 80-kDa nuclear protein was found to bind to the element -TCCTCGTGGGAAGCG- (bases -551 to -537).
- High-fat diet down-regulated GLUT4 minigene mRNA in -701 bp transgenic mice, but not in -551 bp mice, indicating the high-fat-responsive element (HFRE) is located between -701 and -551 bp and is distinct from ASE.
Conclusions:
- The study precisely mapped the adipose tissue-specific element (ASE) and high-fat-responsive element (HFRE) within the GLUT4 gene.
- These regulatory elements are distinct and play crucial roles in controlling GLUT4 expression in adipose tissue.
- Understanding these elements provides insight into the molecular mechanisms underlying diet-induced insulin resistance.