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Energy metabolism in human renin-gene transgenic rats. Does renin contribute to obesity?

Item Type:Article
Title:Energy metabolism in human renin-gene transgenic rats. Does renin contribute to obesity?
Creators Name:Gratze, P. and Boschmann, M. and Dechend, R. and Qadri, F. and Malchow, J. and Graeske, S. and Engeli, S. and Janke, J. and Springer, J. and Contrepas, A. and Plehm, R. and Klaus, S. and Nguyen, G. and Luft, F.C. and Mueller, D.N.
Abstract: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.
Keywords:Renin-Angiotensin System, Obesity, Metabolic Syndrome, ACE Inhibitors, Renin Inhibitors, (Pro)Renin Receptor, Handle Region Peptide, Sprague-Dawley Rats, Transgenic Rats, Animals, Rats
Publisher:American Heart Association
Page Range:516-523
Date:March 2009
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.108.124966
PubMed:View item in PubMed

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