Expression of leptin (Ob) and leptin receptor (Ob-R) in human fibroblasts:Regulation of leptin secretion by insulin

Leptin, a hormone of the cytokine family, is mainly synthesized by white ad ipocytes. As fibroblasts and adipocytes share a common stem cell origin, we hypothesized that connective tissue may be another candidate for leptin sy nthesis. We demonstrated leptin receptors, inclusive of all isoforms, on cu ltured fibroblasts (n = 13) by RT-PCR and immunohistochemistry. In contrast to its receptor, basal leptin mRNA expression and protein secretion were f ound in 8 of 13 cultures, reaching 1.4 ng/350,000 cells.24 h. Incubation wi th physiological insulin concentrations (1 nmol/liter) increased leptin sec retion in fibroblast culture supernatants to 152% of basal levels. A maxima l stimulation of the basal level up to 192% was found with 10 nmol/liter in sulin after 24 h. Actinomycin D and cycloheximide abolished this effect, pr oviding evidence that active RNA and protein synthesis are involved in insu lin's action. Completing these in vitro results, we could show protein expr ession for leptin and leptin receptors in fibroblasts by immunostaining of human skin biopsies in situ. In conclusion, we provide evidence of leptin s ynthesis 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 range s of leptin as well as disruptions in the relationship between fat content and leptin.