title: Adipocytes express a functional system for serotonin synthesis, reuptake and receptor activation.
abstract: OBJECTIVE
  Serotonergic pathways in the central nervous system (CNS) are activated in the regulation of food intake and body weight. We hypothesized that adipocytes, like other cells of mesenchymal origin, possess serotonin receptors and thus could be regulated by peripherally circulating serotonin.
  
  
  METHODS
  In vivo studies: four Sprague-Dawley rats were given daily serotonin (5HT) injections subcutaneously (s.c., 25 mg/kg) for 5 days; four controls received saline. In a long-term study, 12 rats were given serotonin s.c. for 4 months, 10 controls received saline. Body weight was registered throughout the studies, and visceral adipose tissue and plasma were collected and analysed. Adipocytes were isolated from normal rat visceral abdominal adipose tissue and analysed for the expression of serotonin receptors, the serotonin transporter (5HTT/SERT), activation of serotonin synthesis (tryptophan hydroxylase 1, Tph1) and secretion and serotonin-induced leptin regulation by RT-PCR and protein analyses.
  
  
  RESULTS
  Hyperserotoninergic rats had significantly lower body weight (-7.4 and -6.8%) and plasma leptin levels (-44 and -38%) than controls, after both short- and long-term serotonin treatment, respectively, whereas plasma ghrelin levels were unaffected. Compared to controls, serotonin induced a 40-fold upregulation of 5HTT mRNA in visceral adipose tissue after 5 days of treatment. In vitro experiments showed that adipocytes express serotonin receptors, Tph1 and 5HTT, synthesize and secrete serotonin and that serotonin regulates leptin in mature adipocytes.
  
  
  CONCLUSIONS
  These findings show that serotonin may regulate 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. kamilla.stunes@ntnu.no
authors.forename: A K
authors.initials: AK
authors.lastname: Stunes
authors.forename: J E
authors.initials: JE
authors.lastname: Reseland
authors.forename: O
authors.initials: O
authors.lastname: Hauso
authors.forename: M
authors.initials: M
authors.lastname: Kidd
authors.forename: K
authors.initials: K
authors.lastname: Tømmerås
authors.forename: H L
authors.initials: HL
authors.lastname: Waldum
authors.forename: U
authors.initials: U
authors.lastname: Syversen
authors.forename: B I
authors.initials: BI
authors.lastname: Gustafsson
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004435:Eating / Q000187:drug effects; D005260:Female; D007279:Injections, Subcutaneous; D010865:Pilot Projects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin