Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet.
The renin-angiotensin system (RAS) is functional within adipose tissue and angiotensin II, the active component of RAS, has been implicated in adipose tissue hypertrophy and insulin resistance. In this study, captopril, an angiotensin converting enzyme (ACE) inhibitor that prevents angiotensin II formation, was used to study the development of diet-induced obesity and insulin resistance in obesity prone C57BL/6J mice. The mice were fed a high fat diet (w/w 21% fat) and allowed access to either water or water with captopril added (0.2 mg/ml). Body weight was recorded weekly and water and food intake daily. Glucose tolerance was determined after 11-12 weeks. On completion of the study (after 16 weeks of treatment), the mice were killed and kidney, liver, epididymal fat and extensor digitorum longus muscle (EDL) were weighed. Blood samples were collected and plasma analysed for metabolites and hormones. Captopril treatment decreased body weight in the first 2 weeks of treatment. Food intake of captopril-treated mice was similar to control mice prior to weight loss and was decreased after weight loss. Glucose tolerance was improved in captopril-treated mice. Captopril-treated mice had less epididymal fat than control mice. Relative to body weight, captopril-treated mice had increased EDL weight. Relative to control mice, mice administered captopril had a higher plasma concentration of adiponectin and lower concentrations of leptin and non-esterified fatty acids (NEFA). The results indicate that captopril both induced weight loss and improved insulin sensitivity. Thus, captopril may eventually be used for the treatment of obesity and Type 2 diabetes.
Weisinger
Richard S
RS
School of Psychological Science, La Trobe University, Victoria 3086, Australia. r.weisinger@latrobe.edu.au
Stanley
Tracy K
TK
Begg
Denovan P
DP
Weisinger
Harrison S
HS
Spark
Kylie J
KJ
Jois
Markandeya
M
D017667:Adipocytes / Q000187:drug effects / Q000648:ultrastructure; D052242:Adiponectin / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D048429:Cell Size; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D018149:Glucose Intolerance / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006728:Hormones / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000502:physiology
D052242:Adiponectin; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D002216:Captopril