title: Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance.
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.
authors.affiliation: Dean's Ganglion, Centre for Neuroscience, Department of Physiology, and Royal Melbourne Hospital, Faculty of Medicine, and Howard Florey Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Anura P
authors.initials: AP
authors.lastname: Jayasooriya
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mathai
authors.forename: Lesley L
authors.initials: LL
authors.lastname: Walker
authors.forename: Denovan P
authors.initials: DP
authors.lastname: Begg
authors.forename: Derek A
authors.initials: DA
authors.lastname: Denton
authors.forename: David
authors.initials: D
authors.lastname: Cameron-Smith
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKinley
authors.forename: Paula D
authors.initials: PD
authors.lastname: Rodger
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sinclair
authors.forename: John D
authors.initials: JD
authors.lastname: Wark
authors.forename: Harrison S
authors.initials: HS
authors.lastname: Weisinger
authors.forename: Mark
authors.initials: M
authors.lastname: Jois
authors.forename: Richard S
authors.initials: RS
authors.lastname: Weisinger
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000201:enzymology; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002151:Calorimetry; D004326:Drinking; D004734:Energy Metabolism; D005243:Feces / Q000737:chemistry; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006728:Hormones / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000201:enzymology; D051379:Mice; D008954:Models, Biological; D009043:Motor Activity; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency*; D010805:Physical Conditioning, Animal
chemical_list: D006728:Hormones; D007703:Peptidyl-Dipeptidase A; D005947:Glucose