{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:27:29Z","timestamp":1792301249612,"version":"4.4.0"},"reference-count":206,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the European Union\u2019s Horizon 2020 research and innovation program","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"the European Union\u2019s Horizon 2020 research and innovation program","award":["101057014"],"award-info":[{"award-number":["101057014"]}]},{"name":"Horizon Europe, the European Union\u2019s 2021\u20132027 framework program for the funding of research and innovation","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Horizon Europe, the European Union\u2019s 2021\u20132027 framework program for the funding of research and innovation","award":["101057014"],"award-info":[{"award-number":["101057014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The liver is the central metabolic organ of the body. The plethora of anabolic and catabolic pathways in the liver is tightly regulated by physiological signaling but may become imbalanced as a consequence of malnutrition or exposure to certain chemicals, so-called metabolic endocrine disrupters, or metabolism-disrupting chemicals (MDCs). Among different metabolism-related diseases, obesity and non-alcoholic fatty liver disease (NAFLD) constitute a growing health problem, which has been associated with a western lifestyle combining excessive caloric intake and reduced physical activity. In the past years, awareness of chemical exposure as an underlying cause of metabolic endocrine effects has continuously increased. Within this review, we have collected and summarized evidence that certain environmental MDCs are capable of contributing to metabolic diseases such as liver steatosis and cholestasis by different molecular mechanisms, thereby contributing to the metabolic syndrome. Despite the high relevance of metabolism-related diseases, standardized mechanistic assays for the identification and characterization of MDCs are missing. Therefore, the current state of candidate test systems to identify MDCs is presented, and their possible implementation into a testing strategy for MDCs is discussed.<\/jats:p>","DOI":"10.3390\/ijms24032686","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:29:03Z","timestamp":1675218543000},"page":"2686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-5822","authenticated-orcid":false,"given":"Kristin","family":"Fritsche","sequence":"first","affiliation":[{"name":"German Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Zikov\u00e1-Kloas","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment, Department Pesticides Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-2153","authenticated-orcid":false,"given":"Philip","family":"Marx-Stoelting","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment, Department Pesticides Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Braeuning","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1210\/en.2005-1129","article-title":"Environmental obesogens: Organotins and endocrine disruption via nuclear receptor signaling","volume":"147","author":"Grun","year":"2006","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mce.2009.02.018","article-title":"Endocrine disrupters as obesogens","volume":"304","author":"Grun","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.reprotox.2016.10.001","article-title":"Metabolism disrupting chemicals and metabolic disorders","volume":"68","author":"Heindel","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12940-015-0042-7","article-title":"Parma consensus statement on metabolic disruptors","volume":"14","author":"Heindel","year":"2015","journal-title":"Environ. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/nrendo.2017.51","article-title":"Endocrine-disrupting chemicals and the regulation of energy balance","volume":"13","author":"Nadal","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.stem.2014.04.010","article-title":"Stem\/progenitor cells in liver development, homeostasis, regeneration, and reprogramming","volume":"14","author":"Miyajima","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nrg3941","article-title":"Exploring the emerging complexity in transcriptional regulation of energy homeostasis","volume":"16","author":"Lempradl","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrendo.2012.258","article-title":"The role of hepatokines in metabolism","volume":"9","author":"Stefan","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1038\/emm.2015.122","article-title":"Regulation of glucose metabolism from a liver-centric perspective","volume":"48","author":"Han","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_10","first-page":"1","article-title":"Triglyceride Metabolism in the Liver","volume":"8","author":"Cohen","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/cphy.c130024","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cannon, W.B. (1915). Bodily Changes in Pain, Hunger, Fear, and Rage: An Account of Recent Researches into the Function of Emotional Excitement, D. Appleton and Company.","DOI":"10.1037\/10013-000"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1176\/jnp.10.2.230a","article-title":"A syndrome produced by diverse nocuous agents","volume":"10","author":"Selye","year":"1998","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cbi.2004.01.006","article-title":"Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes","volume":"147","author":"You","year":"2004","journal-title":"Chem. Biol. Interact."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tem.2018.01.002","article-title":"Bilirubin in the Liver-Gut Signaling Axis","volume":"29","author":"Hamoud","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Garcia, M., Thirouard, L., Sedes, L., Monrose, M., Holota, H., Caira, F., Volle, D.H., and Beaudoin, C. (2018). Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113630"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"BSR20181061","DOI":"10.1042\/BSR20181061","article-title":"Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism","volume":"38","author":"Lv","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Janah, L., Kjeldsen, S., Galsgaard, K.D., Winther-Sorensen, M., Stojanovska, E., Pedersen, J., Knop, F.K., Holst, J.J., and Wewer Albrechtsen, N.J. (2019). Glucagon Receptor Signaling and Glucagon Resistance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133314"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/j.molmet.2017.04.011","article-title":"The glucoregulatory actions of leptin","volume":"6","author":"Neumann","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"a009191","DOI":"10.1101\/cshperspect.a009191","article-title":"Insulin receptor signaling in normal and insulin-resistant states","volume":"6","author":"Boucher","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"969137","DOI":"10.1155\/2014\/969137","article-title":"Sustained Liver Glucose Release in Response to Adrenaline Can Improve Hypoglycaemic Episodes in Rats under Food Restriction Subjected to Acute Exercise","volume":"2014","author":"Babata","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1042\/BST20180250","article-title":"Amino acid transporters in the regulation of insulin secretion and signalling","volume":"47","author":"Javed","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.3748\/wjg.v18.i46.6771","article-title":"Hepatic expression and cellular distribution of the glucose transporter family","volume":"18","author":"Karim","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"G194","DOI":"10.1152\/ajpgi.00413.2005","article-title":"Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake: Possible role in steatosis","volume":"290","author":"Bradbury","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1126\/science.3513311","article-title":"A receptor-mediated pathway for cholesterol homeostasis","volume":"232","author":"Brown","year":"1986","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0092-8674(95)90200-7","article-title":"The RXR heterodimers and orphan receptors","volume":"83","author":"Mangelsdorf","year":"1995","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1210\/er.2001-0038","article-title":"The nuclear pregnane X receptor: A key regulator of xenobiotic metabolism","volume":"23","author":"Kliewer","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.1128\/MCB.18.10.5652","article-title":"The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene","volume":"18","author":"Honkakoski","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.biochi.2016.12.019","article-title":"The role and regulation of the peroxisome proliferator activated receptor alpha in human liver","volume":"136","author":"Kersten","year":"2017","journal-title":"Biochimie"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1074\/jbc.M110.138115","article-title":"Role of peroxisome proliferator-activated receptor \u03b4\/\u03b2 in hepatic metabolic regulation","volume":"286","author":"Liu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1172\/JCI119424","article-title":"Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids","volume":"99","author":"Considine","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s12020-014-0384-x","article-title":"Adipogenic changes of hepatocytes in a high-fat diet-induced fatty liver mice model and non-alcoholic fatty liver disease patients","volume":"48","author":"Pan","year":"2015","journal-title":"Endocrine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1530\/JOE-16-0447","article-title":"Hepatocyte-specific, PPARgamma-regulated mechanisms to promote steatosis in adult mice","volume":"232","author":"Majumdar","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.tem.2012.05.001","article-title":"PPARs at the crossroads of lipid signaling and inflammation","volume":"23","author":"Wahli","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9768","DOI":"10.1074\/jbc.M610072200","article-title":"Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver","volume":"282","author":"Nakamura","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1124\/mol.107.041012","article-title":"Regulatory cross-talk between drug metabolism and lipid homeostasis: Constitutive androstane receptor and pregnane X receptor increase Insig-1 expression","volume":"73","author":"Roth","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1739","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":"Wang","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1530\/EJE-19-0811","article-title":"Genetics in Endocrinology: Glucocorticoid resistance syndrome","volume":"182","author":"Vitellius","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_39","first-page":"184","article-title":"Thyroid hormone receptors: Multiple forms, multiple possibilities","volume":"14","author":"Lazar","year":"1993","journal-title":"Endocr. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1074\/jbc.M115.668673","article-title":"Hepatic FOXO1 Target Genes Are Co-regulated by Thyroid Hormone via RICTOR Protein Deacetylation and MTORC2-AKT Protein Inhibition","volume":"291","author":"Singh","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/s41598-020-80637-y","article-title":"Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis","volume":"11","author":"Shukla","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mce.2017.07.035","article-title":"Insights into the role of hepatocyte PPAR\u03b1 activity in response to fasting","volume":"471","author":"Regnier","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1136\/gutjnl-2015-310798","article-title":"Liver PPAR\u03b1 is crucial for whole-body fatty acid homeostasis and is protective against NAFLD","volume":"65","author":"Montagner","year":"2016","journal-title":"Gut"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1475-2891-13-17","article-title":"Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications\u2014A review","volume":"13","year":"2014","journal-title":"Nutr. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1172\/JCI200420468","article-title":"PPAR\u03b1 governs glycerol metabolism","volume":"114","author":"Patsouris","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature13961","article-title":"Nutrient-sensing nuclear receptors coordinate autophagy","volume":"516","author":"Lee","year":"2014","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nm.3159","article-title":"PPAR\u03b3 signaling and metabolism: The good, the bad and the future","volume":"19","author":"Ahmadian","year":"2013","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.plipres.2016.09.002","article-title":"Oxysterols: From cholesterol metabolites to key mediators","volume":"64","author":"Mutemberezi","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1172\/JCI0216388","article-title":"Do oxysterols control cholesterol homeostasis?","volume":"110","author":"Bjorkhem","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1101\/gad.844900","article-title":"Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXR\u03b1 and LXR\u03b2","volume":"14","author":"Repa","year":"2000","journal-title":"Genes Dev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/cphy.c120023","article-title":"Bile acid metabolism and signaling","volume":"3","author":"Chiang","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1161\/01.ATV.0000178994.21828.a7","article-title":"The Farnesoid X receptor: A molecular link between bile acid and lipid and glucose metabolism","volume":"25","author":"Claudel","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1172\/JCI21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"Watanabe","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1194\/jlr.M600342-JLR200","article-title":"Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase","volume":"47","author":"Matsukuma","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"26913","DOI":"10.1074\/jbc.M111.248203","article-title":"Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure","volume":"286","author":"Watanabe","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23158","DOI":"10.1074\/jbc.M314322200","article-title":"Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1","volume":"279","author":"Yamagata","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1210\/en.2004-0965","article-title":"Regulation of carbohydrate metabolism by the farnesoid X receptor","volume":"146","author":"Stayrook","year":"2005","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Han, C.Y. (2018). Update on FXR Biology: Promising Therapeutic Target?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072069"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1210\/en.2017-00525","article-title":"FOX01 Is the Headline Akt Regulating Hepatic Glucose Metabolism","volume":"158","author":"Smith","year":"2017","journal-title":"Endocrinology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF00429772","article-title":"Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice","volume":"14","author":"Coleman","year":"1978","journal-title":"Diabetologia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.2337\/db10-0074","article-title":"Disruption of hepatic leptin signaling protects mice from age- and diet-related glucose intolerance","volume":"59","author":"Huynh","year":"2010","journal-title":"Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/hep.26043","article-title":"A role for hepatic leptin signaling in lipid metabolism via altered very low density lipoprotein composition and liver lipase activity in mice","volume":"57","author":"Huynh","year":"2013","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"567","DOI":"10.5483\/BMBRep.2013.46.12.248","article-title":"CREB and FoxO1: Two transcription factors for the regulation of hepatic gluconeogenesis","volume":"46","author":"Oh","year":"2013","journal-title":"BMB Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13163","DOI":"10.1073\/pnas.1411571111","article-title":"Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPAR\u03b3 signaling pathway","volume":"111","author":"Li","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Altosaar, K., Balaji, P., Bond, R.A., Bylund, D.B., Cotecchia, S., Devost, D., Doze, V.A., Eikenburg, D.C., Gora, S., and Goupil, E. (2021). Adrenoceptors (version 2021.3). IUPHAR\/BPS Guide Pharmacol. CITE, 2021.","DOI":"10.2218\/gtopdb\/F4\/2021.3"},{"key":"ref_66","unstructured":"Lennarz, W.J., and Lane, M.D. (2013). Encyclopedia of Biological Chemistry, Academic Press. [2nd ed.]."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/nm788","article-title":"Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase","volume":"8","author":"Yamauchi","year":"2002","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.beem.2013.09.003","article-title":"Adiponectin receptors: A review of their structure, function and how they work","volume":"28","author":"Yamauchi","year":"2014","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.cmet.2013.12.003","article-title":"\u03b2-Aminoisobutyric acid induces browning of white fat and hepatic \u03b2-oxidation and is inversely correlated with cardiometabolic risk factors","volume":"19","author":"Roberts","year":"2014","journal-title":"Cell Metab."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tanianskii, D.A., Jarzebska, N., Birkenfeld, A.L., O\u2019Sullivan, J.F., and Rodionov, R.N. (2019). Beta-Aminoisobutyric Acid as a Novel Regulator of Carbohydrate and Lipid Metabolism. Nutrients, 11.","DOI":"10.3390\/nu11030524"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0303-7207(00)00237-9","article-title":"Alpha2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor","volume":"164","author":"Mathews","year":"2000","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"448","DOI":"10.5551\/jat.No950","article-title":"High glucose induces transactivation of the \u03b12-HS glycoprotein gene through the ERK1\/2 signaling pathway","volume":"16","author":"Takata","year":"2009","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s00125-015-3634-4","article-title":"Hepatokines: Unlocking the multi-organ network in metabolic diseases","volume":"58","author":"Iroz","year":"2015","journal-title":"Diabetologia"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bourebaba, L., and Marycz, K. (2019). Pathophysiological Implication of Fetuin-A Glycoprotein in the Development of Metabolic Disorders: A Concise Review. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122033"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.cmet.2019.01.004","article-title":"A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21","volume":"29","author":"Kliewer","year":"2019","journal-title":"Cell Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.2337\/db14-0595","article-title":"Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding","volume":"63","author":"Markan","year":"2014","journal-title":"Diabetes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"Kharitonenkov","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-nutr-071816-064800","article-title":"Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis","volume":"38","author":"BonDurant","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1172\/JCI74915","article-title":"FGF21 is an endocrine signal of protein restriction","volume":"124","author":"Laeger","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cmet.2010.09.015","article-title":"A liver-derived secretory protein, selenoprotein P, causes insulin resistance","volume":"12","author":"Misu","year":"2010","journal-title":"Cell Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/hep.22526","article-title":"Selenoprotein P expression is controlled through interaction of the coactivator PGC-1\u03b1 with FoxO1a and hepatocyte nuclear factor 4\u03b1 transcription factors","volume":"48","author":"Speckmann","year":"2008","journal-title":"Hepatology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.3390\/nu5061937","article-title":"The relationship between selenoprotein P and glucose metabolism in experimental studies","volume":"5","author":"Mao","year":"2013","journal-title":"Nutrients"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/ng814","article-title":"Angptl3 regulates lipid metabolism in mice","volume":"30","author":"Koishi","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.bbalip.2011.10.010","article-title":"Regulation of triglyceride metabolism by Angiopoietin-like proteins","volume":"1821","author":"Mattijssen","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"21344","DOI":"10.1074\/jbc.M213202200","article-title":"Angiopoietin-like protein 3 mediates hypertriglyceridemia induced by the liver X receptor","volume":"278","author":"Inaba","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mce.2006.05.005","article-title":"Ligand-activated PPAR\u03b2 efficiently represses the induction of LXR-dependent promoter activity through competition with RXR","volume":"256","author":"Matsusue","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nm1214","article-title":"Angiopoietin-related growth factor antagonizes obesity and insulin resistance","volume":"11","author":"Oike","year":"2005","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1172\/JCI117065","article-title":"Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults","volume":"93","author":"Boulware","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1210\/er.2009-0010","article-title":"The role of liver-derived insulin-like growth factor-I","volume":"30","author":"Ohlsson","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1365-2265.2011.04291.x","article-title":"Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH\/IGF-I levels","volume":"77","author":"Fusco","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Adamek, A., and Kasprzak, A. (2018). Insulin-Like Growth Factor (IGF) System in Liver Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051308"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1210\/jc.2018-00740","article-title":"Sex Hormone-Binding Globulin Expression Correlates With Acetyl-Coenzyme A Carboxylase and Triglyceride Content in Human Liver","volume":"104","author":"Hernandez","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.tem.2011.09.005","article-title":"Sex hormone-binding globulin and type 2 diabetes mellitus","volume":"23","author":"Le","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/hep.20784","article-title":"CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice","volume":"42","author":"Wagner","year":"2005","journal-title":"Hepatology"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Hong, F., Pan, S., Guo, Y., Xu, P., and Zhai, Y. (2019). PPARs as Nuclear Receptors for Nutrient and Energy Metabolism. Molecules, 24.","DOI":"10.3390\/molecules24142545"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/383728a0","article-title":"An oxysterol signalling pathway mediated by the nuclear receptor LXR\u03b1","volume":"383","author":"Janowski","year":"1996","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/hep.31296","article-title":"Thyroid Hormone Signaling and the Liver","volume":"72","author":"Ritter","year":"2020","journal-title":"Hepatology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1210\/er.2017-00016","article-title":"Fibroblast Growth Factor 21-Metabolic Role in Mice and Men","volume":"38","author":"Staiger","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1007\/s00125-016-3955-y","article-title":"Glucagon: Acute actions on hepatic metabolism","volume":"59","author":"Miller","year":"2016","journal-title":"Diabetologia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.tem.2017.03.003","article-title":"Unraveling the Regulation of Hepatic Metabolism by Insulin","volume":"28","author":"Titchenell","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/978-1-4939-3609-0_14","article-title":"Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity","volume":"1425","author":"Vinken","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3109\/10408444.2015.1089471","article-title":"The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways","volume":"46","author":"Mellor","year":"2016","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s00204-020-02691-9","article-title":"Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury","volume":"94","author":"Gijbels","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3389\/fendo.2018.00474","article-title":"Metabolic Effects of the Intracellular Regulation of Thyroid Hormone: Old Players, New Concepts","volume":"9","author":"Cicatiello","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"152850","DOI":"10.4061\/2011\/152850","article-title":"Why can insulin resistance be a natural consequence of thyroid dysfunction?","volume":"2011","author":"Brenta","year":"2011","journal-title":"J. Thyroid Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/fcp.12300","article-title":"Is bisphenol A an environmental obesogen?","volume":"31","author":"Legeay","year":"2017","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.tiv.2012.03.017","article-title":"Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells","volume":"26","author":"Huc","year":"2012","journal-title":"Toxicol. In Vitro"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/hep.24685","article-title":"Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver","volume":"55","author":"Marmugi","year":"2012","journal-title":"Hepatology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1210\/en.2016-1479","article-title":"Dysregulated Autophagy in Hepatocytes Promotes Bisphenol A-Induced Hepatic Lipid Accumulation in Male Mice","volume":"158","author":"Yang","year":"2017","journal-title":"Endocrinology"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Garcia-Arevalo, M., Alonso-Magdalena, P., Rebelo Dos Santos, J., Quesada, I., Carneiro, E.M., and Nadal, A. (2014). Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100214"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s00125-013-2944-7","article-title":"Hepatic DNA methylation modifications in early development of rats resulting from perinatal BPA exposure contribute to insulin resistance in adulthood","volume":"56","author":"Ma","year":"2013","journal-title":"Diabetologia"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.chemosphere.2018.08.076","article-title":"Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring","volume":"212","author":"Meng","year":"2018","journal-title":"Chemosphere"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00253-012-4195-9","article-title":"Fungal cytochrome P450 sterol 14\u03b1-demethylase (CYP51) and azole resistance in plant and human pathogens","volume":"95","author":"Becher","year":"2012","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.reprotox.2012.05.099","article-title":"Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides","volume":"34","author":"Jacobsen","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Plant Protection Products and their Residues (PPR Panel) (2009). Scientific Opinion on Risk Assessment for a Selected Group of Pesticides from the Triazole Group to Test Possible Methodologies to Assess Cumulative Effects from Exposure through Food from these Pesticides on Human Health. EFSA J., 7, 1167.","DOI":"10.2903\/j.efsa.2009.1167"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1007\/s00204-016-1925-2","article-title":"Hepatotoxic effects of cyproconazole and prochloraz in wild-type and hCAR\/hPXR mice","volume":"91","author":"Ganzenberg","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00204-019-02445-2","article-title":"Pregnane X receptor mediates steatotic effects of propiconazole and tebuconazole in human liver cell lines","volume":"93","author":"Knebel","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"111283","DOI":"10.1016\/j.fct.2020.111283","article-title":"An adverse outcome pathway-based approach to assess steatotic mixture effects of hepatotoxic pesticides in vitro","volume":"139","author":"Lichtenstein","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Marx-Stoelting, P., Knebel, C., and Braeuning, A. (2020). The Connection of Azole Fungicides with Xeno-Sensing Nuclear Receptors, Drug Metabolism and Hepatotoxicity. Cells, 9.","DOI":"10.3390\/cells9051192"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects","volume":"29","author":"Sunderland","year":"2019","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_121","unstructured":"Stockholm Convention (2022, November 23). Stockholm Convention (Decision SC-4\/17). Available online: http:\/\/chm.pops.int\/Implementation\/IndustrialPOPs\/PFOS\/Overview\/tabid\/5221\/Default.aspx."},{"key":"ref_122","unstructured":"EU (2022, December 14). Commission Delegated Regulation (EU) 2020\/784 of 8 April 2020 Amending Annex I to Regulation (EU) 2019\/1021 of the European Parliament and of the Council as Regards the Listing of Perfluorooctanoic acid (PFOA), Its Salts and PFOA-Related Compounds. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/PDF\/?uri=CELEX:32020R0784&from=EN."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"109402","DOI":"10.1016\/j.ecoenv.2019.109402","article-title":"A review of sources, multimedia distribution and health risks of novel fluorinated alternatives","volume":"182","author":"Wang","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.toxlet.2013.01.025","article-title":"In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths","volume":"218","author":"Buhrke","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.bbagen.2012.03.010","article-title":"PFOS-induced hepatic steatosis, the mechanistic actions on beta-oxidation and lipid transport","volume":"1820","author":"Wan","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tox.2016.12.007","article-title":"Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis","volume":"378","author":"Das","year":"2017","journal-title":"Toxicology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"104700","DOI":"10.1016\/j.tiv.2019.104700","article-title":"Activation of human nuclear receptors by perfluoroalkylated substances (PFAS)","volume":"62","author":"Behr","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1038\/srep04582","article-title":"PFOS induced lipid metabolism disturbances in BALB\/c mice through inhibition of low density lipoproteins excretion","volume":"4","author":"Wang","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1007\/s00204-020-02808-0","article-title":"Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) increase triglyceride levels and decrease cholesterogenic gene expression in human HepaRG liver cells","volume":"94","author":"Louisse","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s00204-020-02732-3","article-title":"Impairment of bile acid metabolism by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in human HepaRG hepatoma cells","volume":"94","author":"Behr","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"11029","DOI":"10.1038\/srep11029","article-title":"Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice","volume":"5","author":"Yan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1289\/ehp.93100259","article-title":"Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: Progress and problems","volume":"100","author":"Safe","year":"1993","journal-title":"Environ. Health Perspect."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/toxsci\/kfl055","article-title":"The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds","volume":"93","author":"Birnbaum","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1080\/07853890310008224","article-title":"Drug-activated nuclear receptors CAR and PXR","volume":"35","author":"Honkakoski","year":"2003","journal-title":"Ann. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.taap.2009.12.003","article-title":"PCB153-elicited hepatic responses in the immature, ovariectomized C57BL\/6 mice: Comparative toxicogenomic effects of dioxin and non-dioxin-like ligands","volume":"243","author":"Kopec","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/toxsci\/kfv215","article-title":"PCB126-Induced Disruption in Gluconeogenesis and Fatty Acid Oxidation Precedes Fatty Liver in Male Rats","volume":"149","author":"Gadupudi","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.taap.2018.10.011","article-title":"Polychlorinated biphenyl exposures differentially regulate hepatic metabolism and pancreatic function: Implications for nonalcoholic steatohepatitis and diabetes","volume":"363","author":"Shi","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.aquatox.2017.01.014","article-title":"Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153","volume":"185","author":"Yadetie","year":"2017","journal-title":"Aquat. Toxicol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Mesnier, A., Champion, S., Louis, L., Sauzet, C., May, P., Portugal, H., Benbrahim, K., Abraldes, J., Alessi, M.C., and Amiot-Carlin, M.J. (2015). The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128847"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/j.jnutbio.2013.01.009","article-title":"Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6\/J mice","volume":"24","author":"Wahlang","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/hep.1840040331","article-title":"Phthalate esters and their effect on the liver","volume":"4","author":"Ganning","year":"1984","journal-title":"Hepatology"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/15376516.2016.1273427","article-title":"The effects of di 2-ethyl hexyl phthalate (DEHP) on cellular lipid accumulation in HepG2 cells and its potential mechanisms in the molecular level","volume":"27","author":"Zhang","year":"2017","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1124\/mol.108.053702","article-title":"Di(2-ethylhexyl) phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant CAR2","volume":"75","author":"DeKeyser","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1289\/ehp.0901217","article-title":"The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPAR\u03b1-dependent mechanisms","volume":"118","author":"Feige","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/toxsci\/kfm096","article-title":"An aryl hydrocarbon receptor odyssey to the shores of toxicology: The Deichmann Lecture, International Congress of Toxicology-XI","volume":"98","author":"Okey","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.taap.2007.12.029","article-title":"Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver","volume":"229","author":"Sato","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1053\/j.gastro.2010.03.033","article-title":"A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis","volume":"139","author":"Lee","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.envint.2013.10.006","article-title":"Environmental concentration of nonylphenol alters the development of urogenital and visceral organs in avian model","volume":"62","author":"Roig","year":"2014","journal-title":"Environ. Int."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.ntt.2011.09.009","article-title":"Developmental toxicity of the environmental pollutant 4-nonylphenol in zebrafish","volume":"33","author":"Chandrasekar","year":"2011","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.toxrep.2015.10.006","article-title":"Effects of 4-nonylphenol on oxidant\/antioxidant balance system inducing hepatic steatosis in male rat","volume":"2","author":"Kourouma","year":"2015","journal-title":"Toxicol. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Yu, J., Yang, X., Luo, Y., Yang, X., Yang, M., Yang, J., Zhou, J., Gao, F., He, L., and Xu, J. (2017). Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180218"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jinorgbio.2018.11.002","article-title":"Organotins in obesity and associated metabolic disturbances","volume":"191","author":"Tinkov","year":"2019","journal-title":"J. Inorg. Biochem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1289\/ehp.1205701","article-title":"Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice","volume":"121","author":"Sahu","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/tox.20531","article-title":"Tributyltin causes obesity and hepatic steatosis in male mice","volume":"26","author":"Zuo","year":"2011","journal-title":"Environ. Toxicol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1210\/me.2005-0367","article-title":"Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates","volume":"20","author":"Grun","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.bcp.2010.12.023","article-title":"Tributyltin chloride induces ABCA1 expression and apolipoprotein A-I-mediated cellular cholesterol efflux by activating LXRalpha\/RXR","volume":"81","author":"Cui","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Lyssimachou, A., Santos, J.G., Andre, A., Soares, J., Lima, D., Guimaraes, L., Almeida, C.M., Teixeira, C., Castro, L.F., and Santos, M.M. (2015). The Mammalian \u201cObesogen\u201d Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143911"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Stossi, F., Dandekar, R.D., Johnson, H., Lavere, P., Foulds, C.E., Mancini, M.G., and Mancini, M.A. (2019). Tributyltin chloride (TBT) induces RXRA down-regulation and lipid accumulation in human liver cells. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224405"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Qiao, X., Li, Y., Mai, J., Ji, X., and Li, Q. (2018). Effect of Dibutyltin Dilaurate on Triglyceride Metabolism through the Inhibition of the mTOR Pathway in Human HL7702 Liver Cells. Molecules, 23.","DOI":"10.3390\/molecules23071654"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1383-5718(01)00240-6","article-title":"Aryl hydrocarbon receptor-mediated activity of mutagenic polycyclic aromatic hydrocarbons determined using in vitro reporter gene assay","volume":"497","author":"Machala","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.1038\/s41598-018-24403-1","article-title":"Co-exposure to benzo[a]pyrene and ethanol induces a pathological progression of liver steatosis in vitro and in vivo","volume":"8","author":"Bucher","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4396403","DOI":"10.1155\/2018\/4396403","article-title":"Possible Involvement of Mitochondrial Dysfunction and Oxidative Stress in a Cellular Model of NAFLD Progression Induced by Benzo[a]pyrene\/Ethanol CoExposure","volume":"2018","author":"Bucher","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.toxlet.2013.09.017","article-title":"In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective","volume":"223","author":"Ortiz","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"111884","DOI":"10.1016\/j.fct.2020.111884","article-title":"Mixture effects of food-relevant polycyclic aromatic hydrocarbons on the activation of nuclear receptors and gene expression, benzo[a]pyrene metabolite profile and DNA damage in HepaRG cells","volume":"147","author":"Goedtke","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.mce.2009.02.024","article-title":"Environmental estrogens and obesity","volume":"304","author":"Newbold","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1017\/S2040174415000033","article-title":"Prenatal diethylstilbestrol exposure and risk of obesity in adult women","volume":"6","author":"Hatch","year":"2015","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.taap.2012.06.003","article-title":"The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice","volume":"263","author":"Hao","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_168","first-page":"1367","article-title":"Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP","volume":"18","author":"Vega","year":"2014","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s12020-015-0732-5","article-title":"Adrenal steroidogenesis disruption caused by HDL\/cholesterol suppression in diethylstilbestrol-treated adult male rat","volume":"52","author":"Haeno","year":"2016","journal-title":"Endocrine"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/hep.1840040310","article-title":"Early hepatic histologic alterations among chemical (vinyl monomer) workers","volume":"4","author":"Tamburro","year":"1984","journal-title":"Hepatology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jat.2550140411","article-title":"Vinyl chloride","volume":"14","author":"Easter","year":"1994","journal-title":"J. Appl. Toxicol."},{"key":"ref_172","unstructured":"U.S. EPA (2000). IRIS Toxicological Review of Vinyl Chloride (Final Report)."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/hep4.1151","article-title":"Vinyl chloride dysregulates metabolic homeostasis and enhances diet-induced liver injury in mice","volume":"2","author":"Lang","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"101205","DOI":"10.1016\/j.redox.2019.101205","article-title":"Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis: Protection by the ALDH2 activator Alda-1","volume":"24","author":"Chen","year":"2019","journal-title":"Redox Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"114730","DOI":"10.1016\/j.taap.2019.114730","article-title":"Role of endoplasmic reticulum stress and oxidative stress in vinyl chloride-induced hepatic steatosis in mice","volume":"381","author":"Wang","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.tox.2013.09.004","article-title":"In vitro endocrine disruption potential of organophosphate flame retardants via human nuclear receptors","volume":"314","author":"Kojima","year":"2013","journal-title":"Toxicology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1021\/acs.chemrestox.9b00058","article-title":"Organophosphorus Flame Retardants Impair Intracellular Lipid Metabolic Function in Human Hepatocellular Cells","volume":"32","author":"Hao","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"117855","DOI":"10.1016\/j.envpol.2021.117855","article-title":"An adverse outcome pathway based in vitro characterization of novel flame retardants-induced hepatic steatosis","volume":"289","author":"Negi","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.etap.2014.08.007","article-title":"Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats","volume":"38","author":"Lasram","year":"2014","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cca.2004.03.009","article-title":"Hyperglycemia associated with increased hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase in rats following subchronic exposure to malathion","volume":"137","author":"Abdollahi","year":"2004","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"108802","DOI":"10.1016\/j.biopha.2019.108802","article-title":"Role of cadmium and arsenic as endocrine disruptors in the metabolism of carbohydrates: Inserting the association into perspectives","volume":"114","author":"Sabir","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1126\/science.183.4129.1094","article-title":"Persistence of cadmium-induced metabolic changes in liver and kidney","volume":"183","author":"Singhal","year":"1974","journal-title":"Science"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"147182","DOI":"10.1016\/j.scitotenv.2021.147182","article-title":"Cadmium chloride induces non-alcoholic fatty liver disease in rats by stimulating miR-34a\/SIRT1\/FXR\/p53 axis","volume":"784","author":"Alshehri","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"115855","DOI":"10.1016\/j.taap.2021.115855","article-title":"Whole life exposure to low dose cadmium alters diet-induced NAFLD","volume":"436","author":"Young","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"115009","DOI":"10.1016\/j.taap.2020.115009","article-title":"Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens","volume":"398","author":"Franco","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"29725","DOI":"10.1074\/jbc.M109.042143","article-title":"Aryl hydrocarbon receptor facilitates DNA strand breaks and 8-oxo-2\u2019-deoxyguanosine formation by the aldo-keto reductase product benzo[a]pyrene-7,8-dione","volume":"284","author":"Park","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/toxsci\/kfv149","article-title":"Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice","volume":"147","author":"Go","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Niture, S., Gadi, S., Lin, M., Qi, Q., Niture, S.S., Moore, J.T., Bodnar, W., Fernando, R.A., Levine, K.E., and Kumar, D. (2023). Cadmium modulates steatosis, fibrosis, and oncogenic signaling in liver cancer cells by activating notch and AKT\/mTOR pathways. Environ. Toxicol.","DOI":"10.1002\/tox.23731"},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"European Chemical Agency (ECHA) and European Food Safety Authority (EFSA) with the technical support of the Joint Research Centre (JRC), Andersson, N., Arena, M., Auteri, D., Barmaz, S., Grignard, E., Kienzler, A., Lepper, P., Lostia, A.M., and Munn, S. (2018). Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528\/2012 and (EC) No 1107\/2009. EFSA J., 16, e05311.","DOI":"10.2903\/j.efsa.2018.5311"},{"key":"ref_190","unstructured":"OECD (2018). Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents, OECD."},{"key":"ref_191","unstructured":"OECD (2008). Test No. 407: Repeated Dose 28-Day Oral Toxicity Study in Rodents, OECD."},{"key":"ref_192","unstructured":"Greaves, P. (2012). Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, Elsevier Academic Press Inc.. [4th ed.]."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3109\/10408444.2013.835786","article-title":"Mode of action and human relevance analysis for nuclear receptor-mediated liver toxicity: A case study with phenobarbital as a model constitutive androstane receptor (CAR) activator","volume":"44","author":"Elcombe","year":"2014","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10408444.2013.835784","article-title":"Mode of action framework analysis for receptor-mediated toxicity: The peroxisome proliferator-activated receptor alpha (PPAR\u03b1) as a case study","volume":"44","author":"Corton","year":"2014","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1007\/s00204-022-03338-7","article-title":"Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver","volume":"96","author":"Sprenger","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/bmc.1279","article-title":"Metabonomic profiling of liver metabolites by gas chromatography-mass spectrometry and its application to characterizing hyperlipidemia","volume":"24","author":"Gu","year":"2010","journal-title":"Biomed. Chromatogr."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrm3314","article-title":"Innovation: Metabolomics: The apogee of the omics trilogy","volume":"13","author":"Patti","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1007\/s00204-015-1602-x","article-title":"Application of omics data in regulatory toxicology: Report of an international BfR expert workshop","volume":"89","author":"Braeuning","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/978-1-0716-0385-7_14","article-title":"The Glucose Tolerance Test in Mice","volume":"2128","author":"Pedro","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-1-4939-2929-0_17","article-title":"Glucose and Insulin Tolerance Tests in the Mouse","volume":"1339","author":"Vinue","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_201","unstructured":"(2022, November 23). Society for Advancement of AOPs. AOP-Wiki. Available online: http:\/\/aopwiki.org."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/acs.chemrestox.8b00112","article-title":"Adverse Outcome Pathway-Driven Analysis of Liver Steatosis in Vitro: A Case Study with Cyproconazole","volume":"31","author":"Luckert","year":"2018","journal-title":"Chem. Res. Toxicol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"111690","DOI":"10.1016\/j.fct.2020.111690","article-title":"Transcript and protein marker patterns for the identification of steatotic compounds in human HepaRG cells","volume":"145","author":"Lichtenstein","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_204","unstructured":"European Chemical Agency (2017). Read-Across Assessment Framework (RAAF), ECHA-17-R-01-EN."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"a000588","DOI":"10.1101\/mcs.a000588","article-title":"Metabolomics: An emerging but powerful tool for precision medicine","volume":"1","author":"Clish","year":"2015","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.chemosphere.2018.10.196","article-title":"Hepatic metabolomics reveals that liver injury increases PCB 126-induced oxidative stress and metabolic dysfunction","volume":"217","author":"Deng","year":"2019","journal-title":"Chemosphere"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:17Z","timestamp":1760120357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,31]]},"references-count":206,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032686"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032686","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,31]]}}}