Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat.
OBJECTIVE
Given the recent observation of a local renin-angiotensin system (RAS) in adipose tissue, and its association with obesity-related hypertension, the metabolic effects of treatment with a low dose angiotensin converting enzyme inhibitor (ACEI) were investigated in a rodent model of diet-induced obesity.


RESULTS
Male Sprague Dawley rats were exposed to either standard laboratory chow (12% calories as fat) or palatable high fat (30% calories as fat) diet for 12 weeks. A subset from both dietary groups was given low dose ACEI in drinking water (perindopril, 0.3 mg/kg/day) throughout the study. The high fat diet increased body weight, adiposity, circulating leptin and insulin and in the liver we observed fat accumulation and increased tissue ACE activity. Treatment with perindopril decreased food intake and circulating insulin in both diet groups, and hepatic ACE activity in high fat fed animals only. Decreased plasma leptin concentration with ACE inhibition was only evident in chow fed animals. These effects were independent of any blood pressure lowering effect of ACE inhibition.


CONCLUSIONS
Chronic low dose ACEI treatment reduced circulating insulin and leptin levels with some reduction in food intake in chow fed rats. Fewer beneficial effects were observed in obesity, and further work is required to investigate higher ACEI doses. Our data suggest a reduction in hepatic ACE activity may affect lipid accumulation and other inflammatory responses, as well as improving insulin resistance. Our findings may have implications for maximizing the clinical benefit of ACEI in patients without overt cardiovascular complications.
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia.
E
E
Velkoska
F J
FJ
Warner
T J
TJ
Cole
I
I
Smith
M J
MJ
Morris
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril