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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 9 4472-4479
Copyright © 2001 by The Endocrine Society


Other Original Articles

Expression of Leptin (Ob) and Leptin Receptor (Ob-R) in Human Fibroblasts: Regulation of Leptin Secretion by Insulin

A. Glasow, W. Kiess, U. Anderegg, A. Berthold, A. Bottner and J. Kratzsch

Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics (A.G., J.K.), and Department of Dermatology, University of Leipzig (U.A.), 04103 Leipzig, Germany; and Children’s Hospital (A.G., W.K., A.Be., A.Bo.), 04317 Leipzig, Germany

Address all correspondence and requests for reprints to: J. Kratzsch, Ph.D., Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig, Liebigstrasse 27, D-04103 Leipzig, Germany. E-mail: kraj{at}medizin.uni-leipzig.de

Abstract

Leptin, a hormone of the cytokine family, is mainly synthesized by white adipocytes. As fibroblasts and adipocytes share a common stem cell origin, we hypothesized that connective tissue may be another candidate for leptin synthesis. We demonstrated leptin receptors, inclusive of all isoforms, on cultured fibroblasts (n = 13) by RT-PCR and immunohistochemistry. In contrast to its receptor, basal leptin mRNA expression and protein secretion were found in 8 of 13 cultures, reaching 1.4 ng/350,000 cells·24 h. Incubation with physiological insulin concentrations (1 nmol/liter) increased leptin secretion in fibroblast culture supernatants to 152% of basal levels. A maximal stimulation of the basal level up to 192% was found with 10 nmol/liter insulin after 24 h. Actinomycin D and cycloheximide abolished this effect, providing evidence that active RNA and protein synthesis are involved in insulin’s action. Completing these in vitro results, we could show protein expression for leptin and leptin receptors in fibroblasts by immunostaining of human skin biopsies in situ. In conclusion, we provide evidence of leptin synthesis and secretion by human fibroblasts that are regulated by insulin. Leptin produced by fibroblasts may thus exert important local autocrine and paracrine actions and contribute to the total plasma pool. Hence it might in part account for variations in body mass index-dependent reference ranges of leptin as well as disruptions in the relationship between fat content and leptin.




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Copyright © 2001 by The Endocrine Society