Adipose tissue macrophage-derived exosomes induce ferroptosis via glutathione synthesis inhibition by targeting SLC7A11 in obesity-induced cardiac injury.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Ferroptosis is an iron-dependent programmed cell death characterized by the accumulation of reactive oxygen species (ROS). Long-term high fat diet (HFD) was found to be associated with ferroptosis and cardiac injury. HFD-induced obesity is characterized by sustained, low-grade inflammation in adipose tissue, while macrophage infiltration plays a crucial role in inflammation. Exosomes (Exos) derived from adipose tissue macrophages (ATMs) participate in the physiological processes of recipient cells. In this study, we investigated the role of ATM-Exos in obesity-induced ferroptosis and cardiac injury. We found that HFD-induced obesity resulted in higher mRNA expression levels of specific markers, e.g., prostaglandin endoperoxide synthase 2 (PTGS2), and increased the levels of lipid peroxides, including malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Macrophages infiltrated the adipose tissues, as examined by flow cytometry. Exosomes derived from ATM-Exos were analyzed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Obese ATM-Exos administration induced higher levels of PTGS2, MDA, 4-HNE, lipid ROS, and mitochondrial injury. Obese ATM-Exos further provoked obvious cardiac injury, demonstrated by abnormal levels of cardiac enzymes and inflammatory factors. Systolic left ventricle (LV) function anomalies were induced by ATM-Exos in obese mi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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