This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by de Kloet, A. D. Articles by Woods, S. C. PubMed PubMed Citation Articles by de Kloet, A. D. Articles by Woods, S. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CAPTOPRIL GLUCOSE

The Effect of Angiotensin-Converting Enzyme Inhibition Using Captopril on Energy Balance and Glucose Homeostasis

Program in Neuroscience (A.D.d.K., R.R.S., R.J.S., S.C.W.) and Department of Psychiatry (E.G.K., D.-H.K., R.R.S., R.J.S., S.C.W.), University of Cincinnati, Cincinnati, Ohio 45237

Address all correspondence and requests for reprints to: Annette D. de Kloet, Program in Neuroscience, University of Cincinnati, 2170 East Galbraith Road, ML0503, Cincinnati, Ohio 45237. E-mail: dekloead{at}uc.edu.

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 (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.