Effects and underlying mechanisms of tetrabromobisphenol A on glucose and lipid metabolism in goldfish.

Fish, one of the most important vertebrates on Earth, are susceptible to glucose and lipid metabolism disorders. Glucose and lipid metabolism in fish are sensitive to environmental contamination; however, the effects of emerging pollutants, such as tetrabromobisphenol A (TBBPA), on these critical processes remain unclear. In this study, the effects and underlying mechanisms of TBBPA on glucose and lipid metabolism were evaluated using goldfish as a representative. Our research showed that in addition to excessive hepatic lipid deposition, TBBPA-exposed goldfish exhibited significantly higher levels of blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and lipid metabolism-related biomarkers, whereas markedly lower hepatic glycogen content and glucose-degrading enzyme activities, indicating a disruption in glucose and lipid metabolism. In addition to TBBPA accumulation in the liver, transcriptomic analysis showed that TBBPA induced hepatic detoxification, which led to the overproduction of reactive oxygen species and reduction of antioxidants, resulting in oxidative damage to the liver. Additionally, TBBPA exposure promoted gut microbiota dysbiosis (with significantly increased proportion of lipopolysaccharide (LPS)-producing Gram-negative bacteria and Firmicutes/Bacteroidetes ratios) and intestinal barrier disruption (reduced goblet cells and increased intestinal malondialdehyde), resulting in elevated concentrations of endotoxin LPS in the intestine and serum, which subsequently activated its specific receptor in the liver and triggered hepatic inflammation. Collectively, our findings indicated that TBBPA disrupts glucose and lipid metabolism in goldfish by inducing oxidative and inflammatory damage to the liver via triggering detoxification as well as disrupting the gut-liver axis.