Impaired adipogenesis in insulin-like growth factor binding protein-1 transgenic mice.
Differentiation of precursor cells into mature fat cells is accompanied by enhanced expression of insulin-like growth factor (IGF)-I and is stimulated by multiple hormones including growth hormone, glucocorticoids, IGF-I and insulin. We used transgenic mice that overexpress insulin-like growth factor binding protein-1 to investigate the role of IGF-I in the accumulation of fat tissue. In response to a sucrose-enriched diet, transgenic mice gained significantly less body weight and the epididymal fat mass was significantly reduced compared with wild-type mice. The increase in adipocyte size was also significantly reduced in transgenic mice compared with wild-type mice. Fewer colonies were generated from adipose tissue from transgenic mice and the mitogenic response of these cells to IGF-I was significantly reduced compared with those from wild-type mice. Induction of glycerol-3-phosphate dehydrogenase, a measure of adipocyte differentiation, by IGF-I but not insulin, was reduced in preadipocytes from transgenic mice. These data indicate that IGF-I has a critical role in the proliferation of adipocyte precursors, the differentiation of preadipocytes and the development of obesity in response to calorie excess.
Rajkumar
K
K
Departments of Internal Medicine & Physiology, University of Manitoba, Winnipeg, R3E 0W3 Canada.
Modric
T
T
Murphy
L J
LJ
D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005947:Glucose / Q000008:administration & dosage; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D005947:Glucose