{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:17:01Z","timestamp":1790011021153,"version":"4.0.1"},"reference-count":28,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"JSPE Future Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:p> The angiotensin II (ANG II)-ANG II type 1 receptor (AT<jats:sub>1<\/jats:sub>R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II\/AT<jats:sub>1<\/jats:sub>R axis via converting ANG II to angiotensin 1\u20137 (Ang 1\u20137), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1\u20137 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300\/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1\u20137 axis represent a potential therapeutic approach to prevent the development of obesity. <\/jats:p>","DOI":"10.1152\/ajpendo.00311.2019","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T12:30:28Z","timestamp":1571833828000},"page":"E1140-E1149","source":"Crossref","is-referenced-by-count":66,"title":["ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue"],"prefix":"10.1152","volume":"317","author":[{"given":"Yasuhiro","family":"Kawabe","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 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