Orange fiber-derived N-methylserotonin reduced myocardial infarct size and cardiac injury biomarkers, improving function by altering adipose exosome lipid composition.
Does N-methylserotonin mitigate myocardial ischemia-reperfusion injury in high-fat diet-fed mice?
Orange fiber-derived N-methylserotonin attenuates myocardial ischemia-reperfusion injury by modulating phytosphingosine in white adipose tissue-derived exosomes.
Absolute Event Rate: 0% vs 0%
Abstract Background White adipose tissue (WAT) exacerbates myocardial ischemia-reperfusion (MI/R) injury via pathological exosome secretion, yet strategies to reprogram these exosomes remain unexplored. N-methylserotonin (N-Me-5HT), a recently identified bioactive compound derived from orange fiber, reduces WAT mass. We hypothesized that N-Me-5HT mitigates MI/R injury by modulating lipid composition in WAT-derived exosomes. Purpose This study aims to investigate whether N-Me-5HT could mitigates MI/R injury and explored the underline mechanism. Methods Three-week oral administration of N-Me-5HT was implemented in high-fat diet-fed C57BL/6J mice to assess its therapeutic effects on MI/R injury. Adipocyte-specific Rab27a knockout mice (AdipoqCre/+-Rab27afl/fl) were generated to block exosome secretion. Untargeted lipidomics and transcriptomics identified key lipid mediators and downstream pathways. Results Administration of N-Me-5HT strikingly reduced infarct size and the expression of cardiac injury biomarkers, while improving cardiac function. These protective effects were abolished in adipocyte-specific Rab27a-knockout mice. In vitro, N-Me-5HT reduce cardiomyocyte apoptosis upon hypoxia/reoxygenation injury. Lipidomics identified that phytosphingosine was the main functional lipid in WAT-derived exosomes. In addition, we further revealed that N-Me-5HT decrease the phytosphingosine in WAT-derived exosomes, which mediated the WAT-cardiomyocyte crosstalk via MAPK pathway in cardiomyocyte to reduce cardiomyocyte apoptosis. Conclusion Orange Fiber-Derived N-Me-5HT attenuated MI/R injury via reprogramming phytosphingosine in WAT-derived exosomes to reduce cardiomyocyte apoptosis, indicating that N-Me-5HT may be a promising translational agent for attenuating MI/R injury.
Chen et al. (Sat,) reported a other. Orange fiber-derived N-methylserotonin reduced myocardial infarct size and cardiac injury biomarkers, improving function by altering adipose exosome lipid composition.