Nitrite is the most common nitrogen-containing compound in nature. It is widely used in food processing like in pickled foods so it has caused widespread public concern about the safety of nitrites due to the formation of nitrosamine, a carcinogen, during the food process. Recent research has shown nitrite has therapeutic potential for cardiovascular disease due to its similar function to NO, yet the safety of oral nitrite and the physiological and biochemical responses induced after oral administration still require further validation. In addition, the relationship between nitrite and glycolipid metabolism still needs to be elucidated. As aquatic animals, fish are more susceptible to nitrite compared to mammals. Herein, we utilized tilapia () as an animal model to explore the relationship between nitrite and glycolipid metabolism in organisms. In the present study, we found that nitrite elicited a hypoxic metabolic response in tilapia and deepened this metabolic response under the co-stress of the pathogenic bacterium (). In addition, nitrite-induced elevation of MetHb (Methemoglobin) and its by-product heme was involved in the metabolic response to nitrite-induced hypoxia through the HO/CO pathway, which has not yet been mentioned in previous studies. Moreover, heme affected hepatic metabolic responses through the ROS-ER stress-VLDL pathway. These findings, for the first time, reveal that nitrite exposure leads to glycolipid metabolic disorder via the heme-HO pathway in teleost. It not only provides new insights into the results of nitrite on the body but also is beneficial for developing healthy strategies for fish farming.

中文翻译：

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亚硝酸盐暴露通过硬骨鱼中的血红素-H2O途径导致糖脂代谢紊乱


亚硝酸盐是自然界中最常见的含氮化合物。它广泛应用于腌制食品等食品加工中，由于在食品加工过程中形成致癌物质亚硝胺，亚硝酸盐的安全性引起了公众的广泛关注。最近的研究表明，亚硝酸盐由于其与NO相似的功能而具有治疗心血管疾病的潜力，但口服亚硝酸盐的安全性以及口服后引起的生理生化反应仍需进一步验证。此外，亚硝酸盐与糖脂代谢之间的关系仍需阐明。作为水生动物，鱼类比哺乳动物更容易受到亚硝酸盐的影响。在此，我们利用罗非鱼作为动物模型来探讨生物体中亚硝酸盐和糖脂代谢之间的关系。在本研究中，我们发现亚硝酸盐会引起罗非鱼的缺氧代谢反应，并在病原菌的共同应激下加深这种代谢反应。此外，亚硝酸盐诱导的MetHb（高铁血红蛋白）及其副产物血红素升高通过H2O/CO途径参与亚硝酸盐诱导的缺氧的代谢反应，这一点在之前的研究中尚未提及。此外，血红素通过 ROS-ER 应激-VLDL 途径影响肝脏代谢反应。这些发现首次揭示了亚硝酸盐暴露通过硬骨鱼中的血红素-H2O途径导致糖脂代谢紊乱。它不仅为亚硝酸盐对身体的影响提供了新的见解，而且有利于制定健康的养鱼策略。