Nitrite exposure leads to glycolipid metabolic disorder via the heme-HO pathway in teleost

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 (Oreochromis niloticus) 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 S.ag (Streptococcus agalactiae). 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.