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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, 0.3 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.

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.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia.

    , , ,

    Source

    MeSH

    Adipose Tissue
    Angiotensin-Converting Enzyme Inhibitors
    Animals
    Blood Glucose
    Blood Pressure
    Body Weight
    Diet
    Dietary Fats
    Energy Intake
    Energy Metabolism
    Insulin
    Leptin
    Lipid Metabolism
    Liver
    Male
    Obesity
    Organ Size
    Peptidyl-Dipeptidase A
    Perindopril
    Rats
    Rats, Sprague-Dawley
    Time Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19361967

    Citation

    Velkoska, E, et al. "Metabolic Effects of Low Dose Angiotensin Converting Enzyme Inhibitor in Dietary Obesity in the Rat." Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, vol. 20, no. 1, 2010, pp. 49-55.
    Velkoska E, Warner FJ, Cole TJ, et al. Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat. Nutr Metab Cardiovasc Dis. 2010;20(1):49-55.
    Velkoska, E., Warner, F. J., Cole, T. J., Smith, I., & Morris, M. J. (2010). Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat. Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, 20(1), pp. 49-55. doi:10.1016/j.numecd.2009.02.004.
    Velkoska E, et al. Metabolic Effects of Low Dose Angiotensin Converting Enzyme Inhibitor in Dietary Obesity in the Rat. Nutr Metab Cardiovasc Dis. 2010;20(1):49-55. PubMed PMID: 19361967.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat. AU - Velkoska,E, AU - Warner,F J, AU - Cole,T J, AU - Smith,I, AU - Morris,M J, Y1 - 2009/04/09/ PY - 2008/10/10/received PY - 2009/02/10/revised PY - 2009/02/10/accepted PY - 2009/4/14/entrez PY - 2009/4/14/pubmed PY - 2010/5/4/medline SP - 49 EP - 55 JF - Nutrition, metabolism, and cardiovascular diseases : NMCD JO - Nutr Metab Cardiovasc Dis VL - 20 IS - 1 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, 0.3 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. 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. SN - 1590-3729 UR - https://www.unboundmedicine.com/medline/citation/19361967/Metabolic_effects_of_low_dose_angiotensin_converting_enzyme_inhibitor_in_dietary_obesity_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-4753(09)00036-2 DB - PRIME DP - Unbound Medicine ER -