What does this research mean for the field?

N-methylserotonin reduces infarct size and cardiac injury biomarkers, improving cardiac function in mice with myocardial ischemia-reperfusion injury. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The study aims to determine if N-methylserotonin mitigates myocardial ischemia-reperfusion injury through modulation of exosomes derived from white adipose tissue.

February 8, 2026

Orange fiber-derived N-methylserotonin reprograms adipose exosomes against ischemia-reperfusion injury

Key Result

Orange fiber-derived N-methylserotonin reduced myocardial infarct size and cardiac injury biomarkers, improving function by altering adipose exosome lipid composition.

Key Points

The study aims to determine if N-methylserotonin mitigates myocardial ischemia-reperfusion injury through modulation of exosomes derived from white adipose tissue.
Three-week oral administration of N-methylserotonin in mice fed a high-fat diet.
Use of adipocyte-specific Rab27a knockout mice to prevent exosome secretion.
Utilization of untargeted lipidomics and transcriptomics to identify key mediators and pathways involved.
N-methylserotonin significantly reduced infarct size and cardiac injury biomarkers while enhancing cardiac function.
Protective effects were lost in Rab27a knockout mice, indicating the role of exosomes.
In vitro analysis showed that N-methylserotonin reduced cardiomyocyte apoptosis during hypoxia/reoxygenation injuries.
Lipidomics identified phytosphingosine as the key lipid in the exosomes and revealed its modulation by N-methylserotonin.

Structured PICO

Does N-methylserotonin mitigate myocardial ischemia-reperfusion injury in high-fat diet-fed mice?

Population

High-fat diet-fed C57BL/6J mice and adipocyte-specific Rab27a knockout mice (AdipoqCre/+-Rab27afl/fl)

Intervention

Three-week oral administration of N-methylserotonin (N-Me-5HT)

Outcome

Infarct size, expression of cardiac injury biomarkers, and cardiac functionsurrogate

Orange fiber-derived N-methylserotonin attenuates myocardial ischemia-reperfusion injury by modulating phytosphingosine in white adipose tissue-derived exosomes.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

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.

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