A. Stunes, J. Reseland, Ø. Hauso, U. Syversen, B. Gustafsson

Serotonergic pathways in the central nervous system (CNS) are activated in the regulation of food intake and body weight. In the search for an efficient treatment of obesity, numerous drugs that interact with the serotonergic system have been developed. In this study we hypothesized that adipocytes, like other cells of mesenchymal origin, possess serotonin receptors, and thus could be regulated by peripherally circulating serotonin.

Using RT-PCR analyses, we found that human, mouse and rat adipocytes express serotonin receptors, the serotonin transporter (5-HTT), and the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1), indicating that adipocytes are able to respond to serotonin and to regulate serotonin availability themselves. In vitro experiments demonstrated that serotonin induces adipocyte proliferation through binding to 5-HT2A/C receptors with subsequent activation of the PKC pathway, and that serotonin regulates synthesis of leptin in mature adipocytes. In vivo experiments showed that hyperserotoninergic Sprague Dawley rats had lower plasma leptin levels than controls, after both short- and long-term serotonin treatment, whereas ghrelin levels were unaffected. Long-term serotonin treated rats had, as expected, a significantly lower body weight than controls.

These findings are of clinical importance as they show that serotonin regulates adipocyte function in a direct manner via the blood circulation and/or paracrine and autocrine mechanisms, and not only indirectly via the CNS as previously assumed.

Disclosures: None