The effect of angiotensin-converting enzyme inhibition using captopril on energy balance and glucose homeostasis.

Increasing evidence suggests that the renin-angiotensin-system contributes to the etiology of obesity. To evaluate the role of the renin-angiotensin-system in energy and glucose homeostasis, we examined body weight and composition, food intake, and glucose tolerance in rats given the angiotensin-converting enzyme inhibitor, captopril ( approximately 40 mg/kg . d). Rats given captopril weighed less than controls when fed a high-fat diet (369.3 +/- 8.0 vs. 441.7 +/- 8.5 g after 35 d; P < 0.001) or low-fat chow (320.1 +/- 4.9 vs. 339.8 +/- 5.1 g after 21 d; P < 0.0001). This difference was attributable to reductions in adipose mass gained on high-fat (23.8 +/- 2.0 vs. 65.12 +/- 8.4 g after 35 d; P < 0.0001) and low-fat diets (12.2 +/- 0.7 vs. 17.3 +/- 1.3 g after 21 d; P < 0.001). Rats given captopril ate significantly less [3110.3 +/- 57.8 vs. 3592.4 +/- 88.8 kcal (cumulative 35 d high fat diet intake); P < 0.001] despite increased in neuropeptide-Y mRNA expression in the arcuate nucleus of the hypothalamus and had improved glucose tolerance compared with free-fed controls. Comparisons with pair-fed controls indicated that decreases in diet-induced weight gain and adiposity and improved glucose tolerance were due, primarily, to decreased food intake. To determine whether captopril caused animals to defend a lower body weight, animals in both groups were fasted for 24 h and subsequently restricted to 20% of their intake for 2 d. When free food was returned, captopril and control rats returned to their respective body weights and elicited comparable hyperphagic responses. These results suggest that angiotensin-converting enzyme inhibition protects against the development of diet-induced obesity and glucose intolerance.