Insulin and TSH signal transduction pathways in human preadipocytes.

Abstract

Signaling through the rapamycin-sensitive mammalian target of rapamycin-p70 S6 kinase (p70 S6K) pathway was examined in human preadipocytes in primary culture. The inhibitory effect of rapamycin on insulin-induced differentiation of preadipose cell lines has been attributed to a blockade of clonal expansion. We demonstrate that rapamycin inhibits the differentiation of human preadipocytes in primary culture, even though these cells do not undergo clonal expansion. Glycerol-3-phosphate-dehydrogenase (GPDH) activity, an indicator of differentiation, was reduced in omental and subcutaneous preadipocytes to 17 +/- 10% (mean +/- 95% confidence limits, n = 10) of standard differentiation. Our data suggest rapamycin-sensitive pathways operate independently of clonal expansion. Our second objective addressed a novel route of p70 S6K activation. We have detected the presence of TSH receptor in human preadipocytes, and have shown it activates PKB and p70 S6K in a wortmannin-sensitive manner. A model depicting the convergence of insulin and TSH signaling in human preadipocytes is proposed.