Potential role of brown adipose tissue-derived extracellular vesicles in mediating the cardioprotective effect of CNS leptin infusion after ischemia/reperfusion injury

Autor: Ana Carolina Mieko Omoto, Ivan Vechetti, Blake Rule, Jussara do Carmo, Alexandre da Silva, Nikaela Aitken, Xuemei Dai, Benjamin Nelson, Zhen Wang, Xuan Li, Alan Mouton, John Hall
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5729450
Popis: Ischemic heart disease is the leading cause of death in the U.S. and worldwide. We recently demonstrated that infusion of leptin into the central nervous system (CNS) dramatically improves cardiac metabolism and function following ischemia/reperfusion (IR) injury. How the brain communicates with the heart during central leptin infusion to improve cardiac function after IR injury is still unknown. One potential mechanism may be via activation of brown adipose tissue (BAT), as central leptin administration has been shown to induce BAT-mediated thermogenesis. Furthermore, BAT has been proposed as an important source of extracellular vesicles (EVs) carrying bioactive molecules with cardioprotective effects. Thus, we investigated whether BAT contributes to the cardioprotective effect of central leptin infusion and the potential role of EVs in this protection. Male Sprague-Dawley rats (~8 weeks of age) were submitted to interscapular BAT ablation (iBATx) and instrumented with an intracerebroventricular (ICV) cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO), myocardial IR was induced by temporary (60 min) ligation of the left anterior descending coronary artery. Vehicle (saline, 0.5 μL/hr) or leptin (0.62 μg/hr) was infused chronically for 28 days starting 30 min after reperfusion using osmotic pumps implanted subcutaneously in the scapular region and connected to the ICV cannula. Cardiac function was assessed weekly by ECHO. Another set of animals with intact iBAT was treated with ICV leptin or vehicle for 2 weeks and had their iBAT collected for EVs isolation and quantification by differential ultracentrifugation and nanoparticle tracking analysis, respectively. Compared to vehicle-treated animals, ICV leptin infusion increases iBAT-derived EVs (5.6x109 vs 1.6 x109 particles/mg of tissue), and removal of iBAT prevent leptin’s CNS-mediated cardioprotective effects after IR injury as indicated by a lack of improvement in ejection fraction (26.9±2.5 vs 40.9±1.2%), stroke volume (154.6±15 vs 275.3±8μL) and global longitudinal strain (-7.4±1.1 vs -13.9±0.5%) at week 4 post-IR. These results suggest that the BAT plays an important role in mediating the cardioprotective effect of CNS leptin administration after I/R injury and that iBAT-derived EVs may be involved in delivering protective molecules to the heart during central leptin infusion. AHA 835218, NIGMS P20GM104357, NIDDK R00DK113280, R01DK121411 and P20GM104320 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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