Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat

Elena Velkoska, F J Warner, Timothy James Cole, Alexander Ian Smith, Margaret J Morris

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND AND AIMS: 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. METHODS AND 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, 0.3mg/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. CONCLUSION: 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.
Original languageEnglish
Pages (from-to)49 - 55
Number of pages6
JournalNutrition Metabolism and Cardiovascular Diseases
Volume20
DOIs
Publication statusPublished - 2010

Cite this

@article{4fed5d3c4e9c469b88e74e7b06db334d,
title = "Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat",
abstract = "BACKGROUND AND AIMS: 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. METHODS AND 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, 0.3mg/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. CONCLUSION: 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.",
author = "Elena Velkoska and Warner, {F J} and Cole, {Timothy James} and Smith, {Alexander Ian} and Morris, {Margaret J}",
year = "2010",
doi = "10.1016/j.numecd.2009.02.004",
language = "English",
volume = "20",
pages = "49 -- 55",
journal = "Nutrition Metabolism and Cardiovascular Diseases",
issn = "0939-4753",
publisher = "Elsevier",

}

Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat. / Velkoska, Elena; Warner, F J; Cole, Timothy James; Smith, Alexander Ian; Morris, Margaret J.

In: Nutrition Metabolism and Cardiovascular Diseases, Vol. 20, 2010, p. 49 - 55.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat

AU - Velkoska, Elena

AU - Warner, F J

AU - Cole, Timothy James

AU - Smith, Alexander Ian

AU - Morris, Margaret J

PY - 2010

Y1 - 2010

N2 - BACKGROUND AND AIMS: 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. METHODS AND 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, 0.3mg/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. CONCLUSION: 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.

AB - BACKGROUND AND AIMS: 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. METHODS AND 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, 0.3mg/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. CONCLUSION: 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.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19361967

U2 - 10.1016/j.numecd.2009.02.004

DO - 10.1016/j.numecd.2009.02.004

M3 - Article

VL - 20

SP - 49

EP - 55

JO - Nutrition Metabolism and Cardiovascular Diseases

JF - Nutrition Metabolism and Cardiovascular Diseases

SN - 0939-4753

ER -