title: The effect of angiotensin-converting enzyme inhibition using captopril on energy balance and glucose homeostasis.
abstract: 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.
authors.affiliation: Program in Neuroscience, University of Cincinnati, Cincinnati, Ohio 45237, USA. dekloead@uc.edu
authors.forename: Annette D
authors.initials: AD
authors.lastname: de Kloet
authors.forename: Eric G
authors.initials: EG
authors.lastname: Krause
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Randall R
authors.initials: RR
authors.lastname: Sakai
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000284:Administration, Oral; D000803:Angiotensin I / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D009765:Obesity / Q000517:prevention & control; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012083:Renin / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004041:Dietary Fats; D009478:Neuropeptide Y; D012333:RNA, Messenger; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D005947:Glucose