Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver illness, is characterized by hepatic steatosis. Exercise and probiotics can regulate the gut microbiota to treat NAFLD; however, their combined effects and the mechanisms of gut-liver communication remain unclear. Inconsistent results on probiotic efficacy further warrant investigation. In this study, zebrafish fed a high-fat diet (HFD) for six weeks were subjected to swimming exercise (HFDE), probiotic intervention (HFDP), or a combination of both (HFDEP) for 10 weeks to explore their effects on NAFLD and the corresponding mechanism. The results showed that NAFLD alleviation followed the order HFDEP > HFDE > HFDP. HFDEP and HFDE treatments effectively reduced Body Mass Index (BMI), relative liver weight, liver vacuolation density, lipid droplets in liver sections, triglyceride, free fatty acid, glucose, and pyruvic acid. In contrast, a single probiotic treatment had limited impact, suggesting a complementary role in NAFLD treatment. Glucose and fatty acid metabolism were central to the “gut–liver” axis. The reduced conversion of glucose to pyruvic acid, decreased fatty acid synthesis and esterification, and accelerated fatty acid transformation to CO₂ contributed to NAFLD improvement under HFDE and HFDEP treatments. This study provides promising theoretical groundwork for potential prevention and treatment strategies for NAFLD.

6:2 Fluorotelomer sulfonate (6:2 FTS), a substitute for perfluorooctane sulfonate (PFOS), is frequently detected in aquatic environments, yet its reproductive toxicity remains incompletely understood. In this study, 480 adult female zebrafish were randomly assigned to five groups: DMSO control, PFOS (0.25 and 5 μg/L), and 6:2 FTS (0.25 and 5 μg/L), with 96 fish per group and three replicate tanks. After 42 days of exposure, PFAS bioaccumulation was assessed using three fish per group; separate sets of six fish per group were used for ovarian oxidative stress, HPG-axis-related hormones, HPG-axis-related gene expression, and reproductive performance; ovarian histopathology was examined using four fish per group; offspring development was assessed using 120 embryos per group; and integrated biomarker response version 2 (IBRv2) was applied. Data are presented as mean ± SEM, with significance set at p < 0.05. Compared with PFOS, 6:2 FTS showed lower bioaccumulation in the maternal liver, ovary, brain, and offspring, but still exhibited relative accumulation in ovarian tissue. Moreover, the ovarian oxidative stress induced by 6:2 FTS was relatively mild. Both compounds disrupted HPG-axis function, increasing gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) levels while decreasing follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2) levels. Consistently, gnrh-family genes and lhβ were upregulated, whereas fshβ and 17β-hsd were downregulated. These endocrine disturbances were associated with abnormal oocyte development, increased follicular atresia, reduced spawning output, and higher offspring malformation risk. IBRv2 analysis indicated that although 6:2 FTS caused lower overall toxicity than PFOS, it still impaired reproduction mainly through HPG-axis disruption. These findings demonstrate the reproductive risk of 6:2 FTS and support careful safety evaluation of PFAS alternatives.

6:2 Chlorinated polyfluoroalkyl ether sulfonate (F-53B) is prevalent in the environment, yet its effect on pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Using adult male zebrafish with high-fat diet-induced MASLD, we investigated the hepatotoxicity of F-53B. Following exposure, F-53B exacerbated hepatic damage in MASLD zebrafish, accelerating progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Notably, environmentally relevant concentrations altered lipid metabolism and MASH/fibrosis markers only in MASLD fish, while high concentrations were required to affect normal-diet fish. This heightened susceptibility stemmed from increased hepatic F-53B accumulation in diseased livers. Mechanistically, liver-type fatty acid-binding protein (L-FABP) knockdown in HepG2 cells reduced lipid accumulation, inflammatory and fibrotic responses, identifying L-FABP as a key F-53B transporter. These findings demonstrate that metabolic dysfunction increases vulnerability to F-53B hepatotoxicity, highlighting the need to consider pre-existing conditions in environmental pollutant risk assessment.