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Considering the increasing environmental contamination of TBBPA analogues and their high structural similarities to the parent compound, whether they could influence adipogenesis or not remains to be elucidated. In this study, two of the most prevalent TBBPA derivatives [i.e., TBBPA bis\u00ad(allyl ether) (TBBPA-BAE) and TBBPA bis\u00ad(2,3-dibromopropyl ether) (TBBPA-BDBPE)] and their byproducts [i.e., TBBPA mono\u00ad(allyl ether) (TBBPA-MAE) and TBBPA mono\u00ad(2,3-dibromopropyl ether) (TBBPA-MDBPE)], together with TBBPA, were screened for their capacities in activating peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) and glucocorticoid receptor (GR), the key nuclear receptors involved in adipogenesis, and their structure-related effects on differentiation of 3T3-L1 preadipocytes were explored. The results indicated that the binding affinities of TBBPA and its analogues for the PPAR\u03b3 ligand-binding domain (PPAR\u03b3-LBD) and GR, as well as their effects on PPAR\u03b3 transactivation, followed the order of TBBPA &amp;gt; TBBPA-MAE &amp;gt; TBBPA-MDBPE &amp;gt; TBBPA-BAE, TBBPA-BDBPE. Nevertheless, TBBPA-MAE and TBBPA-MDBPE showed higher potentials in promoting adipogenesis in 3T3-L1 cells than did TBBPA, as evidenced by intracellular triglyceride contents and adipogenic biomarkers at both protein and transcriptional levels. The etherified group at position 4 of TBBPA phenolic rings was crucial in chemical-induced adipogenic effects, which was related with the recruitment of PPAR\u03b3 and GR-mediated networks and some other unidentified signaling pathways. The findings on the disturbance of TBBPA analogues on adipogenesis revealed their potential risk in causing obesity and other lipid metabolism-related human health concerns.<\/jats:p>","DOI":"10.1021\/acs.est.0c00624","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T08:19:00Z","timestamp":1587457140000},"page":"6262-6271","source":"Crossref","is-referenced-by-count":47,"title":["Chemical Structure-Related Adipogenic Effects of Tetrabromobisphenol\nA and Its Analogues on 3T3-L1 Preadipocytes"],"prefix":"10.1021","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4759-5016","authenticated-orcid":true,"given":"Qian S.","family":"Liu","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Sun","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]},{"name":"University of Chinese Academy of \u200bSciences , , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Ren","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]},{"name":"University of Chinese Academy of \u200bSciences , , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Ren","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]},{"name":"University of Chinese Academy of \u200bSciences , , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Qingdao, P. R. China, 266101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention , , ,","place":["Shenzhen, P. R. China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-100X","authenticated-orcid":true,"given":"Qunfang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]},{"name":"University of Chinese Academy of \u200bSciences , , ,","place":["Beijing, P. R. China, 100049"]},{"name":"University of Chinese Academy of Sciences , , , ,","place":["Hangzhou, P.R. China, 310000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-3917","authenticated-orcid":true,"given":"Guibin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]},{"name":"University of Chinese Academy of \u200bSciences , , ,","place":["Beijing, P. R. China, 100049"]},{"name":"University of Chinese Academy of Sciences , , , ,","place":["Hangzhou, P.R. China, 310000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"2026081418183991300_cit1","doi-asserted-by":"publisher","first-page":"4203","DOI":"10.1021\/acs.est.5b06378","article-title":"Tetrabromobisphenol-A\/S\nand nine novel analogs in biological samples from the Chinese Bohai\nSea: Implications for trophic transfer","volume":"50","author":"Liu","year":"2016","journal-title":"Environ.\nSci. Technol."},{"key":"2026081418183991300_cit2","doi-asserted-by":"publisher","first-page":"4760","DOI":"10.1021\/es3049916","article-title":"Identification\nof tetrabromobisphenol A allyl ether and tetrabromobisphenol\nA 2,3-dibromopropyl ether in the ambient environment near a manufacturing\nsite and in mollusks at a coastal region","volume":"47","author":"Qu","year":"2013","journal-title":"Environ.\nSci. Technol."},{"key":"2026081418183991300_cit3","doi-asserted-by":"publisher","first-page":"5009","DOI":"10.1021\/es2005336","article-title":"Identification of tetrabromobisphenol\nA diallyl ether as an emerging\nneurotoxicant in environmental samples by bioassay-directed fractionation\nand HPLC-APCI-MS\/MS","volume":"45","author":"Qu","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"2026081418183991300_cit4","doi-asserted-by":"publisher","first-page":"13052","DOI":"10.1021\/acs.est.6b02816","article-title":"Emerging and legacy flame retardants\nin UK indoor air and dust: Evidence for replacement of PBDEs by emerging\nflame retardants?","volume":"50","author":"Tao","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"2026081418183991300_cit5","doi-asserted-by":"publisher","first-page":"5434","DOI":"10.1021\/acs.est.7b01071","article-title":"Identification of emerging brominated chemicals as\nthe transformation\nproducts of tetrabromobisphenol A (TBBPA) derivatives in soil","volume":"51","author":"Liu","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"2026081418183991300_cit6","doi-asserted-by":"publisher","first-page":"14361","DOI":"10.1007\/s11356-018-1998-y","article-title":"Review of historical aquatic toxicity and bioconcentration\ndata for the brominated flame retardant tetrabromobisphenol A (TBBPA):\nEffects to fish, invertebrates, algae, and microbial communities","volume":"25","author":"Pittinger","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"2026081418183991300_cit7","doi-asserted-by":"publisher","first-page":"17268","DOI":"10.1007\/s11356-018-2255-0","article-title":"Summary of historical terrestrial\ntoxicity data for\nthe brominated flame retardant tetrabromobisphenol A (TBBPA): Effects\non soil microorganisms, earthworms, and seedling emergence","volume":"25","author":"Rothenbacher","year":"2018","journal-title":"Environ. Sci. Pollut. 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Health Perspect."},{"key":"2026081418183991300_cit17","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1093\/toxsci\/kfx046","article-title":"Thy1 (CD90) expression\nis reduced by the environmental chemical tetrabromobisphenol-A to\npromote adipogenesis through induction of microRNA-103","volume":"157","author":"Woeller","year":"2017","journal-title":"Toxicol. Sci."},{"key":"2026081418183991300_cit18","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/toxsci\/kfu036","article-title":"Halogenated\nbisphenol-A analogs act as obesogens in\nzebrafish larvae (Danio rerio)","volume":"139","author":"Riu","year":"2014","journal-title":"Toxicol. Sci."},{"key":"2026081418183991300_cit19","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1080\/10937404.2011.578561","article-title":"The obesogen hypothesis:\nA shift of focus from the\nperiphery to the hypothalamus","volume":"14","author":"Decherf","year":"2011","journal-title":"J. Toxicol. Environ.\nHealth, Part B"},{"key":"2026081418183991300_cit20","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.tox.2010.08.012","article-title":"Structure-based\ninvestigation on the binding interaction of hydroxylated polybrominated\ndiphenyl ethers with thyroxine transport proteins","volume":"277","author":"Cao","year":"2010","journal-title":"Toxicology"},{"key":"2026081418183991300_cit21","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.taap.2013.01.026","article-title":"Hydroxylated polybrominated\ndiphenyl ethers exhibit different activities on thyroid hormone receptors\ndepending on their degree of bromination","volume":"268","author":"Ren","year":"2013","journal-title":"Toxicol.\nAppl. Pharmacol."},{"key":"2026081418183991300_cit22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.tox.2013.04.001","article-title":"Structure-dependent activities of\nhydroxylated polybrominated diphenyl ethers on human estrogen receptor","volume":"309","author":"Li","year":"2013","journal-title":"Toxicology"},{"key":"2026081418183991300_cit23","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.chemosphere.2016.03.117","article-title":"The potential neurotoxicity\nof emerging tetrabromobisphenol A derivatives\nbased on rat pheochromocytoma cells","volume":"154","author":"Liu","year":"2016","journal-title":"Chemosphere"},{"key":"2026081418183991300_cit24","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jes.2017.05.036","article-title":"Intranasal administration\nof tetrabromobisphenol A bis\u00ad(2-hydroxyethyl ether) induces neurobehavioral\nchanges in neonatal Sprague Dawley rats","volume":"63","author":"Liu","year":"2018","journal-title":"J.\nEnviron. 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Sci. Technol."},{"key":"2026081418183991300_cit41","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1054\/bjoc.1999.1026","article-title":"Relationships between\nhydrophobicity, reactivity, accumulation\nand peripheral nerve toxicity of a series of platinum drugs","volume":"82","author":"Screnci","year":"2000","journal-title":"Br. J. Cancer"},{"key":"2026081418183991300_cit42","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1021\/acs.estlett.6b00138","article-title":"A novel flame retardant\nin the Great Lakes atmosphere: 3,3\u2032,5,5\u2032-tetrabromobisphenol\nA bis\u00ad(2,3-dibromopropyl) ether","volume":"3","author":"Liu","year":"2016","journal-title":"Environ. Sci.\nTechnol. 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