2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of mutagenic/carcinogenic heterocyclic amines (HCAs) found mainly in well-cooked meats. As a common HCAs, IQ can pose a health risk to animals as well as humans. However, to date, few studies have explored IQ's toxic effects on systemic health, and its relevant mechanism of toxicity has not been elucidated. In this study, we for the first time determined IQ accumulation and investigated the tissue damage of developing zebrafish. Zebrafish at one-month post-fertilization were exposed to IQ (80 ng/mL) for 35 days. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis showed that IQ accumulated in multi-organ of zebrafish such as eye, spleen, gonad (ovary or testis), heart, intestine, kidney, muscle, liver, and brain. Our results showed that IQ exposure caused histopathological alterations in IQ-accumulated organs, which could compromise organ function. Exposure to IQ significantly inhibited antioxidant related indicators. Moreover, IQ exposure significantly increased mTOR gene levels. The immunohistochemical results further validated that IQ exposure tended to over activate mTOR. In addition, IQ exposure significantly reduced the expression of autophagy-related genes, and upregulated the expression of DNA damage and repair-related genes, which also detected the accumulation of fluorescence signal of DNA damage marker γ-H2AX. Furthermore, TUNEL assay showed that IQ exposure caused apoptosis. Our findings revealed that IQ could be taken up by developing zebrafish, and accumulate in multiple tissues, especially across the blood-brain barrier, accumulate in the brain, subsequently causing systemic tissue damage, urging us to pay attention to the control or intervention of IQ exposure and decreasing accumulated impairment to systemic health.

Methionine, an essential amino acid, is abundant in animal protein. High dietary methionine intake is associated with the promotion of colorectal cancer (CRC); however, the mechanisms remain unclear. This study aimed to investigate the underlying mechanisms of high dietary methionine promoting CRC and evaluate the effect of high dietary methionine on healthy intestine. Our results demonstrated that high dietary methionine intake exhibited a higher incidence and invasion of tumors in azoxymethane/dextran sulfate sodium-induced mice. Meanwhile, the gut microbiota were disturbed, consequently fostering the metabolism of secondary bile acids. The contents of lithocholic acid and deoxycholic acid significantly increased (P < 0.01), which further activated the bile acid membrane receptors TGR5, and then the activated TGR5 promoted tumor proliferation through STAT3 and YAP pathways. Pseudo-germ-free mice validated the role of gut microbiota and secondary bile acids in promoting CRC by high dietary methionine. Notably, similar disturbances in gut microbiota and bile acid metabolism were observed in the intestine of healthy mice with high dietary methionine intake. In conclusion, dysregulation of bile acid metabolism and activation of the corresponding receptor TGR5 were mechanisms promoting CRC associated with high dietary methionine intake.

Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products (ALEs), which potentially engenders the threat on systemic health or progression of diseases, especially the accumulated effect after long-term intake. Thus, the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion, specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism. The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health, which has been verified by the pathological analysis. Further studies revealed that a high-ALEs diet disrupted the intestinal barrier, with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites. Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency. Furthermore, the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress. Thus, it was revealed that long-term intake of dietary ALE could result in renal impairment, and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.