Table_1_Vitamin K2 Enhances Fat Degradation to Improve the Survival of C. elegans.docx

The beneficial effects of vitamin K (VK) on various chronic age-related syndromes have generally been considered dependent on its antioxidant effects. However, due to the distinct bioavailability and biological activities of VKs, exactly which of these activities and by what mechanisms they might act still need to be elucidated. In this study, we found that VK2 can extend the lifespan of C. elegans and improve the resistance to pathogen infection, heat stress and H2O2-induced inner oxidative stress. Importantly, the roles of VK2 on aging and stress resistance were shown to be dependent on enhanced fat metabolism and not due to its antioxidant effects. Moreover, the genes related to fat metabolism that were up-regulated following VK2 treatment play key roles in improving survival. Obesity is a leading risk factor for developing T2DM, and taking VKs has been previously considered to improve the insulin sensitivity associated with obesity and T2DM risk. However, our results showed that VK2 can significantly influence the expression of genes related to fat metabolism, including those that regulate fatty acid elongation, desaturation, and synthesis of fatty acid-CoA. VK2 enhanced the fatty acid β-oxidation activity in peroxisome to degrade and digest fatty acid-CoA. Our study implies that VK2 can enhance fat degradation and digestion to improve survival, supporting the effectiveness of VK2-based medical treatments. VK2 is mainly produced by gut bacteria, suggesting that VK2 might facilitate communication between the gut microbiota and the host intestinal cells to influence fat metabolism.

维生素K（VK）对多种与年龄相关的慢性综合症的有益效应通常被认为是依赖于其抗氧化作用。然而，鉴于VKs独特的生物利用度和生物学活性，究竟哪些具体活性及其作用机制尚待阐明。在本研究中，我们发现VK2可以延长秀丽线虫的寿命并提高其对病原体感染、热应激和H2O2诱导的内源氧化应激的抵抗力。重要的是，VK2在抗衰老和抗应激方面的作用被证明依赖于脂肪代谢的增强，而非其抗氧化作用。此外，VK2处理后上调的与脂肪代谢相关的基因在提高生存率方面发挥着关键作用。肥胖是导致2型糖尿病（T2DM）的主要风险因素，而摄入VKs曾被视为可以改善与肥胖和T2DM风险相关的胰岛素敏感性。然而，我们的研究结果证实VK2可以显著影响与脂肪代谢相关的基因的表达，包括那些调节脂肪酸延长、不饱和和脂肪酸-CoA合成的基因。VK2增强了过氧化物酶体中的脂肪酸β-氧化活性，以降解和消化脂肪酸-CoA。本研究暗示VK2可以增强脂肪的降解和消化，从而提高生存率，支持基于VK2的医学治疗的有效性。VK2主要由肠道细菌产生，这表明VK2可能促进肠道微生物群与宿主肠道细胞之间的交流，从而影响脂肪代谢。