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 specifically the role of nutrient partitioning in the development of obesity, we overexpressed the insulin-responsive glucose transporter (GLUT4) in 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-fold in brown fat with no overexpression in other tissues. In vivo glucose tolerance was enhanced in transgenic mice. In isolated epididymal, parametrial, and subcutaneous adipose cells from transgenic mice, basal glucose transport was 20-34-fold greater than in nontransgenic littermates. Insulin-stimulated glucose transport was 2-4-fold greater in cells from transgenic mice. Total body lipid was increased 2-3-fold in transgenic mice overexpressing GLUT4 in fat. Surprisingly, fat cell size was unaltered and fat cell number was increased > 2-fold. This is the first animal model in which increased fat mass results solely from adipocyte hyperplasia and it will be a valuable model for understanding the mechanisms responsible for fat cell replication and/or differentiation in vivo.
Shepherd
P R
PR
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts.
Gnudi
L
L
Tozzo
E
E
Yang
H
H
Leach
F
F
Kahn
B B
BB
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004742:Enhancer Elements, Genetic; D004822:Epididymis; D005091:Exons; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D006801:Humans; D006965:Hyperplasia; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins; D011401:Promoter Regions, Genetic; D012737:Sex Factors
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D005947:Glucose