Abstract 1580: Obesity in Human Renin Transgenic Rats - A Novel Role for Human Renin?
Renin is known to function as a protease initiating angiotensin (Ang) II formation. However, we found that transgenic rats over-expressing the human renin gene (TGR(hREN)) develop obesity and feature the metabolic syndrome. We studied these transgenic and non-transgenic control rats (SD) under standard diet for 22 weeks. Body weight (BW) gain was similar in both groups until the age of 7 weeks, although energy expenditure (EE) and lipid oxidation (LOX) were greater in TGR(hREN) vs. SD. Thereafter, BW gain was significantly greater in TGR(hREN) vs. SD. At age 22 weeks, BW was 570±9 g in TGR(hREN) and 497±20 g in SD. Food intake was significantly higher in TGR(hREN) than SD, but EE and LOX were similar in both groups. MRI-determined body composition analysis showed a significantly higher body fat mass in the TGR(hREN) (88±6 g) vs. SD (55±3 g) rats. Additionally, TGR(hREN) had increased serum triglyceride levels (108±8 vs. 66±5 mg/dl) and impaired glucose tolerance tests, compared with SD. Telemetric mean arterial blood pressure was not different in TGR(hREN) and SD (104±2 and 103±2 mm Hg). Chronic ACE inhibitor treatment did not influence BW, triglycerides, or glucose tolerance impairment. When pair-fed, TGR(hREN) rats were restricted to the caloric intake of SD rats, the developed a lower BW than SD. In vitro, we found that neither renin nor renin-inhibitor treatment had any influence on adipogenesis of human preadipocytes. We conclude that renin initiates a process leading to increased appetite, obesity and metabolic alterations independent of blood pressure. Human renin does not seem to have a direct effect on adipogenesis.