Fatty genotype effect on adipocyte lipogenic gene expression: implication of transactivating factors
1996
Rolland, V. | Hainault, I. | Hajduch, E. | Guerre-Millo, M. | Quignard-Boulange, A. | Bazin, R. | Dugail, I. | Lavau, M.
The obesity in the Zucker rat is of autosomal and recessive inheritance and is caused by a single gene mutation (fa for fatty). The nature of this gene remains totally unknown. This rat develops a syndrome that shares many features with human obesity, providing a useful experimental model. An early phenotypic trait that develops in this mutant prior to hyperphagia and prior to hyperinsulinemia is an increase in fat cell size, suggesting the presence in these cells of a "metabolic pull" channeling nutrients into triglycerides. Consistently, a subset of lipid storage enzymes, lipoprotein lipase, glucose transporter GLUT4, glyceraldehyde-3-phosphate dehydrogenase, fatty acid synthase, and malic enzyme, display excessive activity. Studies of the underlying molecular mechanisms showed that the primary responsible step was an overexpression of the genes arising primarily from an increased transcriptional activity. In an attempt to clarify the mechanism by which the increased transcription of these genes is driven in obese rat adipocytes we developed a system of transiently transfected adipocytes using lipogenic gene promoters fused to gene reporters. We provide evidence that promoter activities of glyceraldehyde-3-phosphate dehydrogenase, fatty acid synthetase and glucose transporter GLUT4 were several times higher in adipocytes from obese rats than in those from lean rats, clearly indicating that the fatty mutation affected transcription factors. 5' deletion analysis of glyceraldehyde-3-phosphate dehydrogenase and GLUT4 promoters allowed us to delineate regions critical to the genotype-mediated increase in promoter activities suggesting that they harbor fa-response element(s). The nature of the fa-dependent transactivating factor(s) targeting these fa(RE) remains to be elucidated.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by National Agricultural Library