ADIPOSE CELL HYPERPLASIA AND ENHANCED GLUCOSE DISPOSAL IN TRANSGENIC MICE OVEREXPRESSING GLUT4 SELECTIVELY IN ADIPOSE-TISSUE

To gain insight into the molecular pathogenesis of obesity and specifi cally the role of nutrient partitioning in the development of obesity, we overexpressed the insulin-responsive glucose transporter (GLUT4) i n transgenic mice under the control of the fat-specific aP2 fatty acid -binding protein promoter/enhancer. Two lines of transgenic mice were generated, which overexpressed GLUT4 6-9-fold in white fat and 3-5-fol d in brown fat with no overexpression in other tissues. In vivo glucos e tolerance was enhanced in transgenic mice. In isolated epididymal, p arametrial, and subcutaneous adipose cells from transgenic mice, basal glucose transport was 20-34-fold greater than in nontransgenic litter mates. Insulin-stimulated glucose transport was 2-4-fold greater in ce lls from transgenic mice. Total body lipid was increased 2-3-fold in t ransgenic mice overexpressing GLUT4 in fat. Surprisingly, fat cell siz e was unaltered and fat cell number was increased >2-fold. This is the first animal model in which increased fat mass results solely from ad ipocyte hyperplasia and it will be a valuable model for understanding the mechanisms responsible for fat cell replication and/or differentia tion in vivo.