Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance

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Jayasooriya, Anura P, Mathai, Michael ORCID: 0000-0001-8783-2122, Walker, Lesley L, Begg, Denovan P, Denton, Derek A, Cameron-Smith, David, Egan, Gary F, McKinley, MJ, Rodger, Paula D, Sinclair, Andrew J, Wark, John D, Weisinger, Harrison S, Jois, Mark and Weisinger, Richard S (2008) Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance. Proceedings of the National Academy of Sciences of the United States of America, 105 (18). pp. 6531-6536. ISSN 0027-8424

Abstract

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE−/−) and compared with wild-type littermates. Compared with wild-type littermates, ACE−/− mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE−/− mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE−/− mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE−/− mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Item type Article
URI https://vuir.vu.edu.au/id/eprint/3735
Official URL http://dx.doi.org/10.1073/pnas.0802690105
Subjects Current > Division/Research > Other
Historical > FOR Classification > 0606 Physiology
Historical > FOR Classification > 1101 Medical Biochemistry and Metabolomics
Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Historical > SEO Classification > 970111 Expanding Knowledge in the Medical and Health Sciences
Keywords ResPubID16332, fatty acid metabolism, obesity, ACE knockout mice, glucose tolerance
Citations in Scopus 145 - View on Scopus
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