Subchronic treatment of rats with oxytocin results in improved adipocyte differentiation and increased gene expression of factors involved in adipogenesis

• Published in: British journal of pharmacology 2011-01, Vol.162 (2), p.452-463
• Main Authors: Eckertova, Miroslava, Ondrejcakova, Maria, Krskova, Katarina, Zorad, Stefan, Jezova, Daniela
• Format: Article
• Language: English
• Subjects: adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; adipogenesis; Adipogenesis - drug effects; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; angiogenesis; Animals; Biological and medical sciences; Drug Evaluation, Preclinical; Fatty Acid-Binding Proteins - metabolism; Gene Expression - drug effects; Male; Medical sciences; oxytocin; Oxytocin - blood; Oxytocin - pharmacology; Peptide Elongation Factor 2 - metabolism; Pharmacology. Drug treatments; PPAR gamma - metabolism; protein synthesis; Rats; Rats, Wistar; Research Papers; RNA, Messenger - genetics; Time Factors; white adipose tissue
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.01037.x

BACKGROUND AND PURPOSE Treatment with thiazolidinediones, insulin‐sensitizing drugs, enhances adipogenesis, which may result in unwanted increase in adiposity. Based on the suggested metabolic effects of oxytocin, the aims of the present study were to: (i) determine whether chronic treatment with oxytocin exerts positive effects on white adipose tissue growth without increasing adiposity; (ii) investigate possible mechanisms of action of oxytocin by measuring the level of gene expression of adipogenic factors; and (iii) test the hypothesis that oxytocin's effect on adipose tissue involves specific activation of eukaryotic elongation factor 2 (eEF2). EXPERIMENTAL APPROACH Adult rats were subcutaneously treated with oxytocin (3.6 µg·100 g−1 body weight day−1) via osmotic minipumps for 2 weeks. Adipocytes from epididymal adipose tissue were isolated and their size evaluated by light microscopy. Gene expression of adipogenic and angiogenic factors was determined by real‐time PCR and dephosphorylation of eEF2 by immunoblotting. KEY RESULTS Oxytocin treatment decreased the diameter of adipocytes and increased the epididymal adipose tissue protein content without changing the adipose tissue mass. Increases in fatty acid binding protein, peroxisome proliferator‐activated receptor γ, insulin‐sensitive glucose transporter 4, leptin and CD31 mRNA levels were noted in the epididymal and/or retroperitoneal fat tissue of oxytocin‐treated rats. Oxytocin enhanced the dephosphorylation of eEF2 in the epididymal adipose tissue. CONCLUSIONS AND IMPLICATIONS The present results demonstrate that subchronic treatment with oxytocin induces adipogenic and angiogenic effects and that the eEF2 signalling pathway is involved in these effects of oxytocin on adipose tissue in vivo. These findings are likely to motivate further research and indicate new approaches for modulating adipose tissue morphology and metabolism.