Autocrine IGF-1 action in adipocytes controls systemic IGF-1 concentrations and growth.

Abstract

IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation in vitro. To investigate the role of IGF-1 receptor in vivo, we have inactivated the Igf-1r gene in adipose tissue (IGF-1R(aP2Cre) mice) using conditional gene targeting strategies. 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-1R(aP2Cre) 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. 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.