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

Abstract

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 À1 per day) in drinking water for 26 days. Subjects: In total, 16 male Sprague-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 ± 5.0 g vs 73.0 ± 4.0 g; Po0.05). 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 ± 5.2 g vs 44.4 ± 4.2 g; Po0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (Po0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64 ± 0.56 ng ml À1 ) compared to the untreated group (8.27 ± 1.03 ng ml À1 ; Po0.001). 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.

Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice

“…Among previous studies that reported decreased body weight/body fat with an antagonist of the RAS, several reported decreased food intake 41,42 whereas others did not. 22,43 Therefore, the role of decreased food intake is still to be resolved.…”

Control of Energy Balance by the Brain Renin-Angiotensin System

“…Nonetheless, the relationship between circulating RAS activity and obesity is likely bi-directional. The RAS contributes to energy balance, as genetic [10][11][12][13] and pharmacological [14][15][16][17][18] inhibition of the RAS in rodent models generally results in a negative energy balance (lean animals and/or resistance to weight gain), and chronic elevations in plasma renin activity can lead to obesity [19].…”

Diet-induced Obesity Up-regulates the Abundance of GPR43 and GPR120 in a Tissue Specific Manner

“…In week 11, body composition was determined in rats fed a HFD (n = 9) and control diet (n = 4) by dual energy X-ray absorptiometry as previously described [40]. At the conclusion of week 12, individual body weights were recorded for each animal.…”