Increased body fat in angiotensin converting enzyme 2 (ACE2) knockout mice

Abstract

<p>Background: Angiotensin converting enzyme 2 (ACE2) is a key element of the reninangiotensin system. ACE2 catabolizes the potent vasopressor angiotensin II (Ang II) into the counter regulatory peptide angiotensin (17). Dysregulation of Ang II levels and ACE2 activity play an essential role in cardiovascular disease seen in obesity and type 2 diabetes. Recently, we acquired a novel ACE2 knockout (KO) mouse model. As this is a relatively new model, it was important to characterize the basic metabolic functions of the strain to better plan and interpret future experiments. Aim: To characterize the basic metabolic functions of the ACE2 KO mouse model. Methods: Seven ACE2 KO mice with C57BI/6 background and 7 wild type (WT) littermates were housed with free access to food and water. All mice were fed a high fat chow consisting of 60 % fat. Average daily food and water intake was monitored. Body composition was followed over a period of twelve weeks. Individual body fat, lean mass, free water and total water were measured serially in live mice using an EchoMRI machine (QNMR). Blood glucose was measured using a glucometer. Results: Eight week old ACE2 KO mice showed more body fat (p=0.0362) and higher percent body fat (p=0.0437) versus WT mice. Fed glucose was also elevated (p=0.0146) at baseline in ACE2 KO mice. Twelve weeks of high fat diet caused significant body fat increases in both ACE2 KO and WT mice (p<O.OOl) and blunted differences in body fat between the two groups (p=0.579). Food and water intake were similar throughout. Terminal glucose tolerance testing revealed higher fasting glucose in ACE2 KO mice (p=0.023) and impaired glucose handling with respect to WT mice (p=0.0285). Conclusion: Global loss of ACE2 activity leads to increased body fat and impairment of glucose homeostasis.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 8, 2011</p>