This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 53/3/516    most recent HYPERTENSIONAHA.108.124966v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gratze, P. Articles by Muller, D. N. Search for Related Content PubMed PubMed Citation Articles by Gratze, P. Articles by Muller, D. N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Obesity Related Collections Obesity Animal models of human disease Glucose intolerance

(Hypertension. 2009;53:516.)
© 2009 American Heart Association, Inc.

Original Articles

Energy Metabolism in Human Renin-Gene Transgenic Rats

Does Renin Contribute to Obesity?

Petra Gratze; Michael Boschmann; Ralf Dechend; Fatimunnisa Qadri; Jeanette Malchow; Sabine Graeske; Stefan Engeli; Jürgen Janke; Jochen Springer; Aurelie Contrepas; Ralph Plehm; Susanne Klaus; Genevieve Nguyen; Friedrich C. Luft; Dominik N. Muller

From the Medical Faculty of Charité Campus Buch (M.B., J.M., S.G., S.E., J.J., F.C.L., D.N.M.), Experimental and Clinical Research Center (M.B.), Franz Volhard Clinical Research Center, HELIOS Klinikum Berlin-Buch (P.G., R.D.), Berlin-Buch, Germany; Max Delbrück Center for Molecular Medicine (F.Q., R.P., F.C.L., D.N.M.), Berlin-Buch, Germany; Deutsches Institut für Ernährungsforschung (M.B., S.K.), Potsdam-Rehbrücke, Nuthetal, Germany; Medical Faculty of the Charité (J.S.), Center for Cardiovascular Research, Berlin, Germany; and the Institut National de la Santé et de la Recherche Médicale (A.C., G.N.), Unit 833, Paris, France.

Correspondence to Dominik N. Muller, Max-Delbruck Center for Molecular Medicine and Experimental and Clinical Research Center, Lindenberger Weg 80, 13125 Berlin, Germany. E-mail dominik.mueller{at}mdc-berlin.de

Renin initiates angiotensin II formation and has no other known functions. We observed that transgenic rats (TGR) overexpressing the human renin gene (hREN) developed moderate obesity with increased body fat mass and glucose intolerance compared with nontransgenic Sprague-Dawley (SD) rats. The metabolic changes were not reversed by an angiotensin-converting enzyme inhibitor, a direct renin inhibitor, or by (pro)renin receptor blocker treatment. The obese phenotype in TGR(hREN) originated from higher food intake, which was partly compensated by increases in resting energy expenditure, total thermogenesis (postprandial and exercise activity), and lipid oxidation during the first 8 weeks of life. Once established, the difference in body weight between TGR(hREN) and SD rats remained constant over time. When restricted to the caloric intake of SD, TGR(hREN) developed an even lower body weight than nontransgenic controls. We did not observe significant changes in the cocaine and amphetamine-regulated transcript, pro-opiomelanocortin, both anorexigenic, or neuropeptide Y, orexigenic, mRNA levels in TGR(hREN) versus SD controls. However, the mRNA level of the agouti-related peptide, orexigenic, was significantly reduced in TGR(hREN) versus SD controls at the end of the study, which indicates a compensatory mechanism. We suggest that the human renin transgene initiates a process leading to increased and early appetite, obesity, and metabolic changes not related to angiotensin II. The mechanisms are independent of any currently known renin-related effects.

Key Words: renin-angiotensin system • obesity • metabolic syndrome • ACE inhibitors • renin inhibitors • (pro)renin receptor • handle region peptide