Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

Objective: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. Design: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg&minus;1 per day) in drinking water for 26 days.Subjects: In total, 16 male Sprague&ndash;Dawley rats aged 10 weeks at the start of the study. Measurements: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. Results: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4&plusmn;5.0 g vs 73.0&plusmn;4.0 g; P&lt;0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0&plusmn;5.2 g vs 44.4&plusmn;4.2 g; P&lt;0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (P&lt;0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64&plusmn;0.56 ng ml&minus;1) compared to the untreated group (8.27&plusmn;1.03 ng ml&minus;1; P&lt;0.001). In contrast, there were no differences in lean or bone mass between the two groups.Conclusion: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups<br /