title: Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue.
abstract: The metabolic action of oxytocin has recently been intensively studied to assess the ability of the peptide to regulate energy homeostasis. Despite the obvious weight-reducing effect of oxytocin observed in experimental studies, plasma oxytocin levels were found to be unchanged or even elevated in human obesity. The aim of our study was to evaluate the changes in the oxytocin system in Zucker rats, an animal model closely mirroring morbid obesity in humans. Plasma oxytocin levels were measured in obese Zucker rats and lean controls by enzyme immunoassay after plasma extraction. The expression of oxytocin and oxytocin receptor (OXTR) was assessed at the mRNA and protein levels by quantitative real-time PCR and immunoblotting respectively. Plasma and tissue activity of oxytocinase, the main enzyme involved in oxytocin degradation, were measured by fluorometric assay using an arylamide derivate as the substrate. Obese Zucker rats displayed a marked reduction in plasma oxytocin levels. Elevated liver and adipose tissue oxytocinase activity was noticed in obese Zucker rats. Hypothalamic oxytocin gene expression was not altered by the obese phenotype. OXTR mRNA and protein levels were upregulated in the adipose tissue of obese animals in contrast to the reduced OXTR protein levels in skeletal muscle. Our results show that obesity is associated with reduced plasma oxytocin due to increased peptide degradation by liver and adipose tissue rather than changes in hormone synthesis. This study highlights the importance of the oxytocin system in the pathogenesis of obesity and suggests oxytocinase inhibition as a candidate approach in the therapy of obesity.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia Unit of Physiology, Department of Health Sciences, University of Jaen, 23071 Jaen, Spain Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic Chair of Pharmacology, Jagiellonian University Medical College, 31531 Krakow, Poland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gajdosechova
authors.forename: Katarina
authors.initials: K
authors.lastname: Krskova
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Segarra
authors.forename: Andrea
authors.initials: A
authors.lastname: Spolcova
authors.forename: Maciej
authors.initials: M
authors.lastname: Suski
authors.forename: Rafal
authors.initials: R
authors.lastname: Olszanecki
authors.forename: Stefan
authors.initials: S
authors.lastname: Zorad
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D010122:Cystinyl Aminopeptidase / Q000097:blood; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism*; D010121:Oxytocin / Q000097:blood*; D059748:Proteolysis; D051381:Rats; D011924:Rats, Zucker; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin; D010122:Cystinyl Aminopeptidase
keywords: insulin resistance; obesity; oxytocin; oxytocin receptor; oxytocinase