Abstract P105: ACE2 Activator, Diminazene Aceturate, Reduces Adiposity, but Preserves Lean Mass in Young and Old Rats

Abstract

Obesity is severely debilitating, and increases the risk for cardiovascular events. Recent evidence suggests increased Ang-(1-7)/Mas activity in obese animal models leads to significant reductions in body weight. We hypothesize that activation of ACE2, via Diminazene Aceturate (DIZE), will significantly reduce body weight of both young and aged rats fed 60% high fat diet. Male Fisher 344 x Brown Norway rats, ages 4 (n=12) and 23 months (n=17) were fed 60% high fat diet for one week, whereupon, animals were further divided, and given either 15mg/kg/day DIZE s.c. (Young DIZE, n=6; Old DIZE, n=9) or vehicle (Young Control, n=6; Old Control, n=8). Body weight and food intake were measured throughout the experiment. Time Domain-Nuclear Magnetic Resonance (TD-NMR) was used to assess body composition 1 week and 3 weeks after the start of DIZE treatment. DIZE treatment resulted in a significant reduction of food intake and change in body weight in both young and old animals. TD-NMR results determined the weight-loss was primarily a result of decreased body fat percentage, with a preservation of lean mass as indicated by a reduced fat/lean mass ratio. Tissue weights at the time of sacrifice confirm the significant loss of white adipose tissue (WAT), with no significant difference in tibialis anterior (TA) muscle weights. Importantly, when assessing heart weights, we observed a significant reduction in aged rats treated with DIZE when compared to age matched controls, suggesting a prevention of cardiac hypertrophy associated with obesity. Our data suggests DIZE may be a useful tool in the treatment of obesity along with associated co-morbidities.