{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T06:46:06Z","timestamp":1782542766819,"version":"3.54.5"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.25201.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000}}],"reference-count":63,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["211080"],"award-info":[{"award-number":["211080"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["LMSCorefunding"],"award-info":[{"award-number":["LMSCorefunding"]}]},{"DOI":"10.13039\/100009513","name":"Fondation Acteria","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009513","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns5:p>\n                    Background Despite rising awareness and advances in the field, the prevalence of obesity continues to increase. Current weight-loss treatments are often ineffective long-term, and some are associated with serious side effects. For this reason, alternative pathways need to be explored in order to identify novel pharmacological targets for the treatment of obesity. In this study, we aim to investigate the role of the ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), in the development of obesity and metabolic syndrome. Methods &amp; Results Using global and adipocyte-specific\n                    <ns5:italic>Ahr<\/ns5:italic>\n                    knock-out mouse models, we show that even though global\n                    <ns5:italic>Ahr<\/ns5:italic>\n                    deletion has some protective effects from diet-induced obesity and metabolic syndrome, adipocyte-specific deletion of\n                    <ns5:italic>Ahr<\/ns5:italic>\n                    has no effect. Furthermore, using a variety of techniques to isolate mature adipocytes, such as flotation,\n                    <ns5:italic>in-vitro<\/ns5:italic>\n                    differentiation, and translating ribosome affinity purification, we show no evidence that\n                    <ns5:italic>Ahr<\/ns5:italic>\n                    is expressed in mature white adipocytes. Finally, using single-cell RNA sequencing on cells from a\n                    <ns5:italic>Cyp1a1<\/ns5:italic>\n                    fate reporter mouse line, in which eYFP can be used as a readout of AHR activation, we show that the AHR pathway is active in adipose stem and precursor cells. Using bulk RNA sequencing on adipocyte precursors stimulated with an AHR ligand\n                    <ns5:italic>in-vitro<\/ns5:italic>\n                    , we show evidence suggesting that\n                    <ns5:italic>Ahr<\/ns5:italic>\n                    may be involved in the control of adipocyte differentiation. Conclusions Our study indicates that\n                    <ns5:italic>Ahr<\/ns5:italic>\n                    may play an important role in adipocyte precursors, particularly in the initiation of adipocyte differentiation. We suggest that further investigation into this mechanism may be important to fully elucidate AHR\u2019s effects in obesity.\n                  <\/ns5:p>","DOI":"10.12688\/wellcomeopenres.25201.2","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:19:08Z","timestamp":1782285548000},"page":"114","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mature adipocytes lack functional Aryl Hydrocarbon Receptor \u2013 a study investigating its role in diet-induced obesity in mice"],"prefix":"10.12688","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-1549","authenticated-orcid":false,"given":"Julia","family":"Vlachaki Walker","sequence":"first","affiliation":[{"name":"Faculty of Medicine London England Imperial College London Institute of Clinical Sciences"},{"name":"London England MRC Laboratory of Medical Sciences"},{"name":"London England King's College London Wolfson Sensory, Pain and Regeneration Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Wiggins","sequence":"additional","affiliation":[{"name":"Faculty of Medicine London England Imperial College London Institute of Clinical Sciences"},{"name":"London England MRC Laboratory of Medical Sciences"},{"name":"Immunoregulation Laboratory London England The Francis Crick Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Burke","sequence":"additional","affiliation":[{"name":"Faculty of Medicine London England Imperial College London Institute of Clinical Sciences"},{"name":"London England MRC Laboratory of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Dore","sequence":"additional","affiliation":[{"name":"London England MRC Laboratory of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sardini","sequence":"additional","affiliation":[{"name":"Faculty of Medicine London England Imperial College London Institute of Clinical Sciences"},{"name":"London England MRC Laboratory of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Schiering","sequence":"additional","affiliation":[{"name":"Faculty of Medicine London England Imperial College London Institute of Clinical Sciences"},{"name":"London England MRC Laboratory of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3311-3322","DOI":"10.1242\/jcs.111.22.3311","article-title":"Aryl-Hydrocarbon Receptor is an inhibitory regulator of lipid synthesis and of commitment to adipogenesis.","volume":"111","author":"D Alexander","year":"1998","journal-title":"J Cell Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"105-110","DOI":"10.1289\/ehp.1205421","article-title":"Coplanar Polychlorinated Biphenyls impair glucose homeostasis in lean C57BL\/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice.","volume":"121","author":"N Baker","year":"2013","journal-title":"Environ Health Perspect."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"944-950","DOI":"10.1289\/ehp.1408594","article-title":"Effects of adipocyte Aryl Hydrocarbon Receptor deficiency on PCB-induced disruption of glucose homeostasis in lean and obese mice.","volume":"123","author":"N Baker","year":"2015","journal-title":"Environ Health Perspect."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"21607-21611","DOI":"10.1074\/jbc.C500090200","article-title":"ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription.","volume":"280","author":"T Beischlag","year":"2005","journal-title":"J Biol Chem."},{"key":"ref5","article-title":"MRC London Institute of Medical Sciences: Activation of the Aryl Hydrocarbon Receptor in mature adipocytes does not impact diet-induced obesity in mice. NCBI, BioProject: PRJNA1369970.","year":"2025"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"99-109","DOI":"10.1093\/toxsci\/kfm085","article-title":"Persistent binding of ligands to the Aryl Hydrocarbon Receptor.","volume":"98","author":"J Bohonowych","year":"2007","journal-title":"Toxicol Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"55-59","DOI":"10.1016\/0378-4274(95)03537-0","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibition of fat cell differentiation.","volume":"84","author":"A Brodie","year":"1996","journal-title":"Toxicol Lett."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"146-152","DOI":"10.1002\/j.1550-8528.1997.tb00655.x","article-title":"CCAAT\/enhancer-binding protein beta is not affected by Tetrachlorodibenzo-p-Dioxin (TCDD) inhibition of 3T3-L1 preadipocyte differentiation.","volume":"5","author":"C Chen","year":"1997","journal-title":"Obes Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"22548-22555","DOI":"10.1074\/jbc.270.38.22548","article-title":"Regulation of CYP1A1 by indolo[3,2-b] carbazole in murine hepatoma cells.","volume":"270","author":"Y Chen","year":"1995","journal-title":"J Biol Chem."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1272-1278","DOI":"10.1038\/sj.ijo.0801380","article-title":"Body weight loss increases plasma and adipose tissue concentrations of potentially toxic pollutants in obese individuals.","volume":"24","author":"J Chevrier","year":"2000","journal-title":"Int J Obes Relat Metab Disord."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1732-1739","DOI":"10.1016\/j.jnutbio.2011.12.005","article-title":"Indole-3-carbinol prevents diet-induced obesity through modulation of multiple genes related to adipogenesis, thermogenesis or inflammation in the visceral adipose tissue of mice.","volume":"23","author":"Y Choi","year":"2012","journal-title":"J Nutr Biochem."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"804-814","DOI":"10.1038\/nm.4350","article-title":"Insulin action and resistance in obesity and type 2 diabetes.","volume":"23","author":"M Czech","year":"2017","journal-title":"Nat Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"15019","DOI":"10.1038\/nrdp.2015.19","article-title":"Type 2 diabetes mellitus.","volume":"1","author":"R Defronzo","year":"2015","journal-title":"Nat Rev Dis Primers."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"18504-18515","DOI":"10.1074\/jbc.RA119.009282","article-title":"Aryl hydrocarbon Receptor (AhR) regulates adipocyte differentiation by assembling CRL4B ubiquitin ligase to target PPAR\u03b3 for proteasomal degradation.","volume":"294","author":"H Dou","year":"2019","journal-title":"J Biol Chem."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"249-259","DOI":"10.1016\/j.cmet.2011.02.005","article-title":"Transcriptional control of adipose lipid handling by IRF4.","volume":"13","author":"J Eguchi","year":"2011","journal-title":"Cell Metab."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"937-950","DOI":"10.1016\/j.tcb.2020.09.007","article-title":"Toward a consensus view of mammalian adipocyte stem and progenitor cell heterogeneity.","volume":"30","author":"R Ferrero","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"48-62","DOI":"10.1016\/j.cmet.2015.12.015","article-title":"Obesity and cancer: the oil that feeds the flame.","volume":"23","author":"J Font-burgada","year":"2016","journal-title":"Cell Metab."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"889-894","DOI":"10.1126\/science.1141634","article-title":"A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.","volume":"316","author":"T Frayling","year":"2007","journal-title":"Science."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"dev155861","DOI":"10.1242\/dev.155861","article-title":"PDGFR\u03b1\/PDGFR\u03b2 signaling balance modulates progenitor cell differentiation into white and beige adipocytes.","volume":"145","author":"Z Gao","year":"2018","journal-title":"Development."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"950","DOI":"10.3390\/ijms20040950","article-title":"Inducible loss of the Aryl Hydrocarbon Receptor activates perigonadal white fat respiration and brown fat thermogenesis via fibroblast growth factor 21.","volume":"20","author":"N Girer","year":"2019","journal-title":"Int J Mol Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1029-1036","DOI":"10.1016\/j.toxrep.2014.09.016","article-title":"Estrogen receptor alpha and Aryl Hydrocarbon Receptor cross-talk in a transfected hepatoma cell line (HepG2) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.","volume":"1","author":"M G\u00f6ttel","year":"2014","journal-title":"Toxicol Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"230-239","DOI":"10.1016\/j.cmet.2012.01.010","article-title":"Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells.","volume":"15","author":"R Gupta","year":"2012","journal-title":"Cell Metab."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.3390\/cells12131748","article-title":"Deficiency of Adipose Aryl Hydrocarbon Receptor protects against diet-induced metabolic dysfunction through sexually dimorphic mechanisms.","volume":"12","author":"N Haque","year":"2023","journal-title":"Cells."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"479-488","DOI":"10.1042\/BJ20140582","article-title":"Application of a novel regulatable Cre recombinase system to define the role of liver and gut metabolism in drug oral bioavailability.","volume":"465","author":"C Henderson","year":"2015","journal-title":"Biochem J."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3489","DOI":"10.1038\/s41467-022-31126-5","article-title":"Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR\/STAT3\/IL-6 signaling.","volume":"13","author":"T Huang","year":"2022","journal-title":"Nat Commun."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"75-80","DOI":"10.1016\/j.abb.2018.01.018","article-title":"Suppressive effects of Aryl-Hydrocarbon Receptor repressor on adipocyte differentiation in 3T3-L1 cells.","volume":"642","author":"Y Ishihara","year":"2018","journal-title":"Arch Biochem Biophys."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"241-251","DOI":"10.1210\/en.2006-0692","article-title":"Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression.","volume":"148","author":"J Jager","year":"2007","journal-title":"Endocrinology."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1252-1259","DOI":"10.1289\/ehp.1205003","article-title":"Obesity is mediated by differential Aryl Hydrocarbon Receptor signaling in mice fed a Western diet.","volume":"120","author":"J Kerley-Hamilton","year":"2012","journal-title":"Environ Health Perspect."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"253-263","DOI":"10.1016\/S2213-8587(22)00033-X","article-title":"Body-mass index and risk of obesity-related complex multimorbidity: an observational multicohort study.","volume":"10","author":"M Kivim\u00e4ki","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"45304-45307","DOI":"10.1074\/jbc.C400186200","article-title":"Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).","volume":"279","author":"Y Li","year":"2004","journal-title":"J Biol Chem."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2407-2421","DOI":"10.1038\/s41366-019-0340-1","article-title":"Aryl Hydrocarbon Receptor agonist indigo protects against obesity-related insulin resistance through modulation of intestinal and metabolic tissue immunity.","volume":"43","author":"Y Lin","year":"2019","journal-title":"Int J Obes (Lond)."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"5-13","DOI":"10.1002\/oby.20662","article-title":"Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study.","volume":"22","author":"A Look","year":"2014","journal-title":"Obesity (Silver Spring)."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"120-133","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: from discovery to biology.","volume":"23","author":"R Loos","year":"2022","journal-title":"Nat Rev Genet."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"221-230","DOI":"10.1007\/s00360-005-0483-3","article-title":"Dioxin: a review of its environmental effects and its Aryl Hydrocarbon Receptor biology.","volume":"175","author":"P Mandal","year":"2005","journal-title":"J Comp Physiol B."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"5317-5328","DOI":"10.1128\/MCB.25.13.5317\u20135328.2005","article-title":"Aryl Hydrocarbon Receptor-mediated transcription: ligand-dependent recruitment of estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters.","volume":"25","author":"J Matthews","year":"2005","journal-title":"Mol Cell Biol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"656-666. e1","DOI":"10.1016\/j.cmet.2018.06.019","article-title":"CalR: a web-based analysis tool for indirect calorimetry experiments.","volume":"28","author":"A Mina","year":"2018","journal-title":"Cell Metab."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3122S-3126S","DOI":"10.1093\/jn\/130.12.3122S","article-title":"Adipocyte differentiation and gene expression.","volume":"130","author":"J Ntambi","year":"2000","journal-title":"J Nutr."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"545-550","DOI":"10.1038\/nature01606","article-title":"Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.","volume":"423","author":"F Ohtake","year":"2003","journal-title":"Nature."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"395-402","DOI":"10.1242\/jcs.108.1.395","article-title":"Inhibition of 3T3-L1 adipose differentiation by 2,3,7,8-tetrachlorodibenzo- p-dioxin.","volume":"108","author":"M Phillips","year":"1995","journal-title":"J Cell Sci."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1878-1892.e7","DOI":"10.1016\/j.celrep.2019.10.018","article-title":"Aryl Hydrocarbon Receptor contributes to the transcriptional program of IL-10-producing regulatory B cells.","volume":"29","author":"C Piper","year":"2019","journal-title":"Cell Rep."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"316-327","DOI":"10.1080\/00039896.1971.10665850","article-title":"A health survey of workers in a 2,4-D and 2,4,5-T plan with special attention to chloracne, porphyria cutanea tarda, and psychologic parameters.","volume":"22","author":"A Poland","year":"1971","journal-title":"Arch Environ Health."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3389\/fendo.2020.00259","article-title":"Macrophage subsets in obesity, aligning the liver and adipose tissue.","volume":"11","author":"A Remmerie","year":"2020","journal-title":"Front Endocrinol (Lausanne)."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1048-1061","DOI":"10.1016\/j.celrep.2016.12.087","article-title":"Simultaneous transcriptional and epigenomic profiling from specific cell types within heterogeneous tissues in vivo.","volume":"18","author":"H Roh","year":"2017","journal-title":"Cell Rep."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"45777-45784","DOI":"10.1074\/jbc.M301977200","article-title":"Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects.","volume":"278","author":"V Rotter","year":"2003","journal-title":"J Biol Chem."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6731-6736","DOI":"10.1073\/pnas.93.13.6731","article-title":"Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development.","volume":"93","author":"J Schmidt","year":"1996","journal-title":"Proc Natl Acad Sci U. S. A."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"961-967","DOI":"10.1038\/nature07182","article-title":"PRDM16 controls a brown fat\/skeletal muscle switch.","volume":"454","author":"P Seale","year":"2008","journal-title":"Nature."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"131-137","DOI":"10.1006\/bbrc.1998.9100","article-title":"Depletion of Arylhydrocarbon Receptor during adipose differentiation in 3T3-L1 cells.","volume":"249","author":"S Shimba","year":"1998","journal-title":"Biochem Biophys Res Commun."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-213X-1-4","article-title":"Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.","volume":"1","author":"S Srinivas","year":"2001","journal-title":"BMC Dev Biol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"889923","DOI":"10.3389\/fendo.2022.889923","article-title":"The Regulation of Adipose Tissue Health by Estrogens.","volume":"13","author":"B Steiner","year":"2022","journal-title":"Front Endocrinol (Lausanne)."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"403-432","DOI":"10.1146\/annurev-immunol-032713-120245","article-title":"The Aryl Hydrocarbon Receptor: multitasking in the immune system.","volume":"32","author":"B Stockinger","year":"2014","journal-title":"Annu Rev Immunol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"559-570","DOI":"10.1038\/s41575-021-00430-8","article-title":"AHR in the intestinal microenvironment: safeguarding barrier function.","volume":"18","author":"B Stockinger","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"707-721.e5","DOI":"10.1016\/j.stem.2020.03.004","article-title":"Mosaic mutant analysis identifies PDGFR\u03b1\/PDGFR\u03b2 as negative regulators of adipogenesis.","volume":"26","author":"C Sun","year":"2020","journal-title":"Cell Stem Cell."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"274-287","DOI":"10.1038\/s41574-018-0148-4","article-title":"Mechanisms of weight regain after weight loss - the role of adipose tissue.","volume":"15","author":"M Baak","year":"2019","journal-title":"Nat Rev Endocrinol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"119-132","DOI":"10.1016\/j.cell.2015.03.008","article-title":"The hunger genes: pathways to obesity.","volume":"161","author":"A Klaauw","year":"2015","journal-title":"Cell."},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.17605\/OSF.IO\/DX3FJ","article-title":"Activation of the Aryl Hydrocarbon Receptor in mature adipocytes does not impact diet-induced obesity in mice.","volume":"11","author":"J Vlachaki Walker","year":"2025","journal-title":"OSF."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1739-1744","DOI":"10.1289\/ehp.1103593","article-title":"Aryl Hydrocarbon Receptor deficiency enhances insulin sensitivity and reduces PPAR-\u03b1 pathway activity in mice.","volume":"119","author":"C Wang","year":"2011","journal-title":"Environ Health Perspect."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"39-55","DOI":"10.1016\/s0009-2797(97)00111-7","article-title":"Rapid and transient induction of CYP1A1 gene expression in human cells by the tryptophan photoproduct 6-formylindolo[3,2- b]carbazole.","volume":"110","author":"Y Wei","year":"1998","journal-title":"Chem Biol Interact."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"821-829","DOI":"10.1038\/s41586-023-06508-4","article-title":"Endothelial sensing of AHR ligands regulates intestinal homeostasis.","volume":"621","author":"B Wiggins","year":"2023","journal-title":"Nature."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1843-1855","DOI":"10.1128\/MCB.23.6.1843\u20131855.2003","article-title":"The Aryl Hydrocarbon Receptor mediates degradation of estrogen receptor \u03b1 through activation of proteasomes.","volume":"23","author":"M Wormke","year":"2003","journal-title":"Mol Cell Biol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1300-1309","DOI":"10.1038\/ijo.2015.63","article-title":"Aryl Hydrocarbon Receptor deficiency protects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure.","volume":"39","author":"C Xu","year":"2015","journal-title":"Int J Obes (Lond)."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1700119","DOI":"10.1002\/mnfr.201700119","article-title":"3,3'-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity.","volume":"61","author":"H Yang","year":"2017","journal-title":"Mol Nutr Food Res."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"50230-50236","DOI":"10.1074\/jbc.M200958200","article-title":"Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle.","volume":"277","author":"C Yu","year":"2002","journal-title":"J Biol Chem."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"10703-10708","DOI":"10.1073\/pnas.0403652101","article-title":"Selective disruption of PPAR\u03b32 impairs the development of adipose tissue and insulin sensitivity.","volume":"101","author":"J Zhang","year":"2004","journal-title":"Proc Natl Acad Sci U. 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