Nutrition, Metabolism & Cardiovascular Diseases
Volume 20, Issue 1 , Pages 49-55, January 2010

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

  • E. Velkoska

      Affiliations

    • Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia
    • ,
  • F.J. Warner

      Affiliations

    • Liver Cell Biology, Centenary Institute, Camperdown NSW 2050, Australia
    • ,
  • T.J. Cole

      Affiliations

    • Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
    • ,
  • I. Smith

      Affiliations

    • Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
    • ,
  • M.J. Morris

      Affiliations

    • Department of Pharmacology, School of Medical Sciences, University of New South Wales, Kensington NSW 2052, Australia
    • Corresponding Author InformationCorresponding author. Tel.: +61 2 9385 1560; fax: +61 2 9385 1059.

Received 10 October 2008; received in revised form 10 February 2009; accepted 10 February 2009. published online 10 April 2009.

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.

Keywords: Leptin, Insulin, Liver, Renin-angiotensin system

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☆ This work was presented in abstract form to the International Congress of Obesity, Sydney, September 2006.

PII: S0939-4753(09)00036-2

doi:10.1016/j.numecd.2009.02.004

Nutrition, Metabolism & Cardiovascular Diseases
Volume 20, Issue 1 , Pages 49-55, January 2010

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