{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:25:28Z","timestamp":1790198728491,"version":"4.1.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,2,27]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Cardiovascular disease remains the leading cause of death worldwide, with coronary artery disease being the primary contributor. Our recent studies suggest that activation of LepRs (leptin receptors) in the brain can improve cardiac function after myocardial infarction. However, the mechanism by which this cardioprotective effect is transmitted from the brain to the heart remains unclear. We hypothesize that brain LepR activation stimulates brown adipose tissue (BAT) to secrete extracellular vesicles (EVs) enriched with cardioprotective factors. These EVs may safeguard the heart by modulating cardiac mitochondrial function and collagen deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Sprague-Dawley rats with BAT intact, BAT ablation, or BAT sympathetic denervation were implanted with an intracerebroventricular cannula for continuous leptin or vehicle delivery over 28 days after cardiac ischemia-reperfusion injury. Cardiac function was assessed weekly via echocardiography and by ventricular catheterization at the end of the protocol. EVs were isolated from BAT for analysis. Rab27a (Ras-related protein Rab-27A), a protein required for EV release, was knocked down using adeno-associated virus, and EV tracking was conducted using a double fluorescent reporter mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Our findings indicate that BAT ablation or BAT sympathetic denervation diminishes the cardioprotective effects of brain LepR activation. We also observed an increased concentration of EVs within the BAT of rats treated with intracerebroventricular leptin compared with vehicle-treated controls, an effect abolished by BAT denervation. Furthermore, knockdown of Rab27a in BAT reduced the cardioprotective benefits of brain LepR activation. MicroRNA miR-29c-3p was identified as a cargo of leptin-stimulated BAT-derived EVs and appears to play a key role in mitigating cardiac fibrosis after ischemia-reperfusion injury in leptin-treated animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Activation of LepR in the brain protects the heart after ischemia-reperfusion injury via sympathetic-mediated BAT-derived EVs enriched with miR-29c-3p.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.326878","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:00:32Z","timestamp":1770199232000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Leptin Activates Brain-BAT-Heart Crosstalk to Promote Cardiac Protection"],"prefix":"10.1161","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-7109","authenticated-orcid":true,"given":"Ana C.M.","family":"Omoto","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1024-1011","authenticated-orcid":true,"given":"Ivan","family":"Vechetti","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE (I.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussara M.","family":"do Carmo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8028-8942","authenticated-orcid":true,"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-3071","authenticated-orcid":true,"given":"Alan J.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, 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