Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.

中文翻译：

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恩尼亚汀和白僵菌素对脂质代谢的影响：来自 3D HepaRG 球体模型的见解


新出现的霉菌毒素恩尼汀 (ENN) 和白僵菌素 (BEA) 通过饮食接触对人类构成潜在的健康风险。然而，对其毒性机制的研究有限，缺乏全面的毒理学数据。本研究从肝脏脂质代谢的角度进行研究，建立更精确、更可靠的3D HepaRG肝细胞球体模型作为毒性评估的替代方案。利用生理指标、组织病理学分析、脂质组学和分子对接技术，全面阐明ENNs和BEA对肝脂质稳态的影响及其分子毒理学机制。我们的研究结果表明，ENN 和 BEA 影响细胞活力和生化功能，显着改变脂质代谢途径，特别是涉及甘油磷脂和鞘脂的途径。分子对接证明 ENN 和 BEA 与脂质代谢中的关键酶（例如过氧化物酶体增殖物激活受体 α (PPARα) 和胞浆磷脂酶 A2 (cPLA2)）具有很强的结合亲和力，揭示了它们的肝毒性作用和损害肝功能的潜在机制基础和人类健康。这些见解增强了我们对此类真菌毒素潜在肝毒性的理解，并为评估其健康风险奠定了基础。