{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:21:15Z","timestamp":1790418075921,"version":"4.1.0"},"reference-count":33,"publisher":"Portland Press Ltd.","issue":"17","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Emerging studies have demonstrated that microRNAs (miRs) participate in the development of multiple metabolic complications including cardiovascular diseases. Among them, circulating level of liver-secreted miR-122 was closely correlated with several consequence of heart diseases in clinical studies, and overexpression of miR-122 impaired cardiomyocyte function. However, it was unknown whether miR-122 could regulate cardiac biology in obesity. Therefore, present study was to disclose the role of miR-122 in cardiac metabolic disorders and potential molecular mechanisms. Through utilizing clinical samples and high fat diet-fed mice, we investigated the physiological roles of miR-122 in obesity-related cardiomyopathy. Besides, present study explored the mitochondrial function under exosomal miR-122 stimulation in mouse primary cardiomyocytes. In clinical samples and obese mice, the circulating level of exosomal miR-122 was positively correlated with cardiac dysfunctional parameters, including reduction in ejection fraction (EF) and increased levels of NT-proBNP. Human plasma exosomes transported miR-122 into mouse primary cardiomyocytes, and impaired mitochondrial ATP production and oxygen consumption, whereas miR-122 sponge improved these inhibitory effects. In dietary-induced mice, increased hepatic and circulating exosomal miR-122 deteriorated cardiac structure and functional index, and inhibited mitochondrial function. Liver-specific blockage of miR-122 attenuated abnormal cardiac remodeling. Mechanistically, miR-122 directly bound and suppressed mitochondrial protein ADP-ribosylation factor-like 2 (Arl-2) in vitro and in vivo. Knockdown of Arl-2 abolished the mitochondrial benefits of miR-122 sponge in exosome-treated mouse primary cardiomyocytes.<\/jats:p>\n               <jats:p>In conclusions, our present study firstly showed that liver-secreted exosomal miR-122 played a critical role in the development of metabolic cardiomyopathy, and miR-122\/mitochondrial Arl-2 signaling affected cardiac energy homeostasis.<\/jats:p>","DOI":"10.1042\/cs20190558","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T16:05:16Z","timestamp":1566403516000},"page":"1871-1881","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2"],"prefix":"10.1042","volume":"133","author":[{"given":"Yongshun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, China"},{"name":"Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China"},{"name":"The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pianpian","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, the Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, China"},{"name":"Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China"},{"name":"The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"2021113012315517000_B1","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.2337\/diacare.27.5.1047","article-title":"Global prevalence of diabetes: estimates for the year 2000 and projections for 2030","volume":"27","author":"Wild","year":"2004","journal-title":"Diabetes Care"},{"key":"2021113012315517000_B2","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/S0140-6736(02)09901-4","article-title":"Diet and risk of coronary heart disease and type 2 diabetes","volume":"360","author":"Mann","year":"2002","journal-title":"Lancet"},{"key":"2021113012315517000_B3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.4161\/rna.18827","article-title":"Liver-specific microRNA-122: biogenesis and function","volume":"9","author":"Jopling","year":"2012","journal-title":"RNA Biol."},{"key":"2021113012315517000_B4","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1172\/JCI63539","article-title":"Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver","volume":"122","author":"Hsu","year":"2012","journal-title":"J. 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