Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
Copyright policy )Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
OBJECTIVE—IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation in vitro. RESEARCH DESIGN AND METHODS—To investigate the role of IGF-1 receptor in vivo, we have inactivated the Igf-1r gene in adipose tissue (IGF-1RaP2Cre mice) using conditional gene targeting strategies. RESULTS—Conditional IGF-1R inactivation resulted in increased adipose tissue mass with a predominantly increased lipid accumulation in epigonadal fat pads. However, insulin-stimulated glucose uptake into adipocytes was unaffected by the deletion of the IGF-1R. Surprisingly, IGF-1RaP2Cre mice exhibited markedly increased somatic growth in the presence of elevated IGF-1 serum concentrations, and IGF-1 mRNA expression was significantly increased in liver and adipose tissue. IGF-1 stimulation of wild-type adipocytes significantly decreased IGF-1 mRNA expression, whereas the opposite effect was observed in IGF-1R–deficient adipocytes. CONCLUSIONS—IGF-1R signaling in adipocytes does not appear to be crucial for the development and differentiation of adipose tissue in vivo, but we identified a negative IGF-1R–mediated feedback mechanism of IGF-1 on its own gene expression in adipocytes, indicating an unexpected role for adipose tissue IGF-1 signaling in the regulation of IGF-1 serum concentrations in control of somatic growth.
- University of Cologne Germany
- Leipzig University Germany
Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Body Weight, Gene Expression, Receptor, IGF Type 1, Mice, Inbred C57BL, Eating, Mice, Glucose, Insulin-Like Growth Factor Binding Protein 3, Phenotype, Adipose Tissue, Adipocytes, Animals, RNA, Messenger, Insulin-Like Growth Factor I, Cells, Cultured, Gene Deletion, Signal Transduction
Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Body Weight, Gene Expression, Receptor, IGF Type 1, Mice, Inbred C57BL, Eating, Mice, Glucose, Insulin-Like Growth Factor Binding Protein 3, Phenotype, Adipose Tissue, Adipocytes, Animals, RNA, Messenger, Insulin-Like Growth Factor I, Cells, Cultured, Gene Deletion, Signal Transduction
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