{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:47:09Z","timestamp":1782362829940,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012543","name":"Shanghai Natural Science Foundation","doi-asserted-by":"publisher","award":["23ZR1459600"],"award-info":[{"award-number":["23ZR1459600"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Disciplines in the Three-Year Plan of the Shanghai Municipal Public Health System","award":["GWVI-11.1-41 and 42"],"award-info":[{"award-number":["GWVI-11.1-41 and 42"]}]},{"name":"Key Projects in the Three-Year Plan of the Shanghai Municipal Public Health System","award":["GWVI-4"],"award-info":[{"award-number":["GWVI-4"]}]},{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/National Key Laboratory of Environmental and Health Impact Assessment of New Pollutants"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objective: Bisphenol AF (BPAF), a fluorinated analogue of bisphenol A, is an environmental contaminant associated with hepatotoxicity and metabolic disruption. However, the systematic molecular mechanisms linking early transcriptional events to metabolic dysfunction in the liver remain poorly defined. The aim of this study is to elucidate the association between BPAF exposure and hepatic lipid accumulation by integrating transcriptomics, cellular metabolomics, and targeted phenotypic assays. Methods: We performed RNA-sequencing on livers from mice exposed to BPAF (0.1\u201310 mg\/kg\/day, 28 days), and performed non-targeted metabolomics on AML12 murine hepatocytes co-cultured with RAW264.7 macrophages in a Transwell system (0\u20132500 nM BPAF, 48 h). Key metabolic pathways were identified through integrated bioinformatics and validated using enzymatic assays, qRT-PCR, Western blotting, and phenotypic staining (lipid droplets, ROS). Results: Multi-omics integration revealed significant disruption of PPAR signaling and the tricarboxylic acid (TCA) cycle. A striking dose-dependent accumulation of succinate was observed in exposed cells, concomitant with a significant inhibition of succinate dehydrogenase (SDH) activity (52% reduction at 2500 nM, p &lt; 0.001). Transcriptomic data confirmed the downregulation of mitochondrial fatty acid \u03b2-oxidation genes. Phenotypic validation indicated that BPAF exposure is associated with oxidative stress, pro-inflammatory cytokine release (TNF-\u03b1, IL-6), and pronounced intracellular lipid droplet accumulation in hepatocytes. Conclusions: This study suggests that BPAF exposure is associated with SDH dysfunction, TCA cycle arrest, and lipid dysregulation. Whether BPAF directly inhibits SDH or acts through upstream mitochondrial targets warrants further structural and kinetic investigation.<\/jats:p>","DOI":"10.3390\/metabo16070440","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T03:20:21Z","timestamp":1782357621000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Multi-Omics Links Bisphenol AF (BPAF) Exposure to Hepatic Lipid Metabolism Disruption via Succinate Dehydrogenase Dysfunction and Mitochondrial Impairment"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5330-2218","authenticated-orcid":false,"given":"Ning","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Leng","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Le","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-3874","authenticated-orcid":false,"given":"Da-Sheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Sheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Lei","family":"Qian","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong-Hua","family":"Tao","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xiao","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Hong","sequence":"additional","affiliation":[{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4274\/tjps.galenos.2019.58219","article-title":"Toxicological evaluation of bisphenol A and its analogues","volume":"17","author":"Demir","year":"2020","journal-title":"Turk. 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