{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:27:53Z","timestamp":1783042073792,"version":"3.54.6"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["RGPIN-2017-04768"],"award-info":[{"award-number":["RGPIN-2017-04768"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heart &amp; Stroke Foundation of Canada","award":["G-17-0018361"],"award-info":[{"award-number":["G-17-0018361"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipid overload contributes to cardiac complications of diabetes and obesity. However, the underlying mechanisms remain obscure. This study investigates the role of gamma-aminobutyrate transaminase (ABAT), the key enzyme involved in the catabolism of \u03b3-aminobutyric acid (GABA), in lipid overload-induced cardiac injury. Microarray revealed a down-regulation of ABAT mRNA expression in high fat diet (HFD)-fed mouse hearts, which correlated with a reduction in ABAT protein level and its GABA catabolic activity. Transgenic mice with cardiomyocyte-specific ABAT over-expression (Tg-ABAT\/tTA) were generated to determine the role of ABAT in lipid overload-induced cardiac injury. Feeding with a HFD to control mice for 4 months reduced ATP production and the mitochondrial DNA copy number, and induced myocardial oxidative stress, hypertrophy, fibrosis and dysfunction. Such pathological effects of HFD were mitigated by ABAT over-expression in Tg-ABAT\/tTA mice. In cultured cardiomyocytes, palmitate increased mitochondrial ROS production, depleted ATP production and promoted apoptosis, all of which were attenuated by ABAT over-expression. With the inhibition of ABAT\u2019s GABA catabolic activity, the protective effects of ABAT remained unchanged in palmitate-induced cardiomyocytes. Thus, ABAT protects the mitochondrial function in defending the heart against lipid overload-induced injury through mechanisms independent of its GABA catabolic activity, and may represent a new therapeutic target for lipid overload-induced cardiac injury.<\/jats:p>","DOI":"10.3390\/ijms23042182","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T21:36:24Z","timestamp":1645047384000},"page":"2182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gamma-Aminobutyrate Transaminase Protects against Lipid Overload-Triggered Cardiac Injury in Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Mengxiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China"},{"name":"School of Pharmacy, Bengbu Medical College, Bengbu 233000, China"},{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiting","family":"Zhong","sequence":"additional","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Cao","sequence":"additional","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5905-8165","authenticated-orcid":false,"given":"Yifan","family":"Huang","sequence":"additional","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-8277","authenticated-orcid":false,"given":"Guo-Chang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqing","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Centre, London, ON N6A 5W9, Canada"},{"name":"Department of Medicine, Western University, London, ON N6A 5W9, Canada"},{"name":"VRLA6-140, 800 Commissioners Road, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u20132013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet Lond. 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