{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:59:17Z","timestamp":1791845957650,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fellowship DAAD\/CNPq\/CAPES-Brazil","award":["246794\/2012-7"],"award-info":[{"award-number":["246794\/2012-7"]}]},{"name":"Fellowship DAAD\/CNPq\/CAPES-Brazil","award":["MR\/T031115\/1"],"award-info":[{"award-number":["MR\/T031115\/1"]}]},{"name":"Fellowship DAAD\/CNPq\/CAPES-Brazil","award":["BJT 407352"],"award-info":[{"award-number":["BJT 407352"]}]},{"name":"Fellowship DAAD\/CNPq\/CAPES-Brazil","award":["SFB1365"],"award-info":[{"award-number":["SFB1365"]}]},{"name":"Career Development Award from the Medical Research Council","award":["246794\/2012-7"],"award-info":[{"award-number":["246794\/2012-7"]}]},{"name":"Career Development Award from the Medical Research Council","award":["MR\/T031115\/1"],"award-info":[{"award-number":["MR\/T031115\/1"]}]},{"name":"Career Development Award from the Medical Research Council","award":["BJT 407352"],"award-info":[{"award-number":["BJT 407352"]}]},{"name":"Career Development Award from the Medical Research Council","award":["SFB1365"],"award-info":[{"award-number":["SFB1365"]}]},{"name":"CNPq","award":["246794\/2012-7"],"award-info":[{"award-number":["246794\/2012-7"]}]},{"name":"CNPq","award":["MR\/T031115\/1"],"award-info":[{"award-number":["MR\/T031115\/1"]}]},{"name":"CNPq","award":["BJT 407352"],"award-info":[{"award-number":["BJT 407352"]}]},{"name":"CNPq","award":["SFB1365"],"award-info":[{"award-number":["SFB1365"]}]},{"name":"DFG","award":["246794\/2012-7"],"award-info":[{"award-number":["246794\/2012-7"]}]},{"name":"DFG","award":["MR\/T031115\/1"],"award-info":[{"award-number":["MR\/T031115\/1"]}]},{"name":"DFG","award":["BJT 407352"],"award-info":[{"award-number":["BJT 407352"]}]},{"name":"DFG","award":["SFB1365"],"award-info":[{"award-number":["SFB1365"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Angiotensin converting enzyme 2 (ACE2) presents pleiotropic actions. It hydrolyzes angiotensin I (AngI) and angiotensin II (AngII) into angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), respectively, as well as participates in tryptophan uptake in the gut and in COVID-19 infection. Our aim was to investigate the metabolic effect of ACE2 deletion in young adults and elderly mice under conditions of high calorie intake. Male C57Bl\/6 (WT) and ACE2-deficient (ACE2-\/y) mice were analyzed at the age of 6 and 12 months under standard diet (StD) and high-fat diet (HFD). Under StD, ACE2-\/y showed lower body weight and fat depots, improved glucose tolerance, enhanced insulin sensitivity, higher adiponectin, and lower leptin levels compared to WT. This difference was even more pronounced after HFD in 6-month-old mice, but, interestingly, it was blunted at the age of 12 months. ACE2-\/y presented a decrease in adipocyte diameter and lipolysis, which reflected in the upregulation of lipid metabolism in white adipose tissue through the increased expression of genes involved in lipid regulation. Under HFD, both food intake and total energy expenditure were decreased in 6-month-old ACE2-\/y mice, accompanied by an increase in liquid intake, compared to WT mice, fed either StD or HFD. Thus, ACE2-\/y mice are less susceptible to HFD-induced obesity in an age-dependent manner, as well as represent an excellent animal model of human lipodystrophy and a tool to investigate new treatments.<\/jats:p>","DOI":"10.3390\/ijms25179515","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T12:22:33Z","timestamp":1725366153000},"page":"9515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5751-7751","authenticated-orcid":false,"given":"Val\u00e9ria","family":"Nunes-Souza","sequence":"first","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"},{"name":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife 50670-901, Brazil"},{"name":"National Institute of Science and Technology in Nanobiopharmaceutics (Nanobiofar), Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-5433","authenticated-orcid":false,"given":"Natalia","family":"Alenina","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimunnisa","family":"Qadri","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-532X","authenticated-orcid":false,"given":"Valentina","family":"Mosienko","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"},{"name":"School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8738-5852","authenticated-orcid":false,"given":"Robson Augusto Souza","family":"Santos","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology in Nanobiopharmaceutics (Nanobiofar), Belo Horizonte 31270-901, Brazil"},{"name":"Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Institute for Biology, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9280-6527","authenticated-orcid":false,"given":"Luiza Antas","family":"Rabelo","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"},{"name":"National Institute of Science and Technology in Nanobiopharmaceutics (Nanobiofar), Belo Horizonte 31270-901, Brazil"},{"name":"Laboratory of Cardiovascular Reactivity, Metabolic Syndrome Center, Institute of Biological Sciences and Health, Federal University of Alagoas, Macei\u00f3 57072-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1\u20139","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ. 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