Brown adipose tissue-derived exosomes ameliorate obesity-related hypertension via HuR-mediated restoration of endothelial function.

Abstract

BACKGROUND: Obesity-related hypertension (OH) is driven by endothelial dysfunction, chronic inflammation, and oxidative stress, yet effective targeted therapies are lacking. This study aims to investigate the mechanisms by which brown adipose tissue-derived exosomes (BAT-Exos) improve vascular endothelial function in OH via HuR protein delivery. METHODS: Rat models with OH and palmitic acid-treated endothelial cell injury models were established. BAT-Exos were compared with white adipose tissue-derived exosomes (WAT-Exos) for therapeutic efficacy. In vitro, primary endothelial cells isolated from rat aortas were treated with palmitic acid to induce injury, followed by pre-treatment with BAT-Exos or WAT-Exos. Inflammatory cytokines, adhesion molecules, oxidative stress markers, eNOS activity, and nitric oxide (NO) levels were measured. RESULTS: BAT-Exos exert superior therapeutic effects compared to WAT-Exos in both in vivo and in vitro models of OH. In rat model of high-fat-diet-induced OH, BAT-Exos improved metabolic profiles, lowered blood pressure, and alleviated vascular remodeling, while reducing inflammation and restoring eNOS activity. In vitro, BAT-Exos significantly mitigated palmitic acid-induced endothelial dysfunction by suppressing pro-inflammatory cytokines, adhesion molecules, and oxidative stress markers, while enhancing nitric oxide production. CONCLUSION: These findings confirm HuR as a key therapeutic cargo. The BAT-Exo-HuR axis represents a novel intercellular signaling pathway that improves vascular function and may serve as a promising strategy for treating OH and related cardiovascular disorders.