Abstract

Brown and white adipose tissues contribute differently to cardiovascular risk factors, yet the precise mechanisms remain elusive. Exosomes-tiny vesicles containing ribonucleic acid, proteins and lipids mediate inter-organ communication. We hypothesized that exosomes secreted by brown and white adipose tissues carry distinct microRNA profiles that differentially modulate myocardial ischemia/reperfusion injury. Male rats underwent 30 min left forearm ischemia, followed by reperfusion. Prior to reperfusion, exosomal secretions from brown and white adipose tissues were directly injected into the myocardium. Cardiac function was assessed through echocardiography, Evans blue and 2,3,5-triphenyltetrazolium chloride dual staining, as well as hematoxylin and eosin and Masson trichrome staining. The microRNA content in the adipose tissue-derived exosomes was analyzed using microarray and bioinformatics approaches, followed by quantitative polymerase chain reaction for real-time microRNA expression profiling. Protein levels modulated by microRNA-34c-3p agomir or antagomir were examined using proteomic analysis. Exosomal secretions from brown and white adipose tissues exerted distinct effects on myocardial ischemia/reperfusion injury. Compared to white adipose tissue, exosomes from brown adipose tissue significantly upregulated 55 microRNAs and downregulated 34 microRNAs. Genes involved in various biological processes-such as positive recirculatory aquaculture system signaling regulation, negative target of rapamycin signaling regulation, circadian rhythm mediation, autophagy and FOXO, mitogen-activated protein kinases, and Wnt signaling pathways are targeted by these differentially expressed microRNAs. Most notably, quantitative polymerase chain reaction analyses identified significant increases in microRNA-133a-3p and microRNA-378, and a decrease in microRNA-34c-3p. Further, microRNA-34c-3p agomir treatment led to increased expression of the cardiac gene G protein subunit alpha I3. Exosomes derived from brown and white adipose tissues differentially influence myocardial ischemia/ reperfusion injury, potentially due to distinct microRNA contents. Among them, miR-34c-3p stands out for its role in exacerbating myocardial ischemia/reperfusion injury through its target hub gene, G protein subunit alpha I3.