{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:49:46Z","timestamp":1782114586021,"version":"3.54.5"},"reference-count":82,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of Health","award":["R21CA245492"],"award-info":[{"award-number":["R21CA245492"]}]},{"name":"National Institute of Health","award":["P30 AG028747"],"award-info":[{"award-number":["P30 AG028747"]}]},{"name":"National Institute of Health","award":["R21AG084142"],"award-info":[{"award-number":["R21AG084142"]}]},{"DOI":"10.13039\/100019823","name":"University of Maryland, Baltimore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019823","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019822","name":"Institute for Clinical and Translational Research, University of Maryland, Baltimore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019822","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["1UL1TR003098"],"award-info":[{"award-number":["1UL1TR003098"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["P30CA134274"],"award-info":[{"award-number":["P30CA134274"]}]},{"DOI":"10.13039\/100024327","name":"Maryland Department of Health","doi-asserted-by":"crossref","award":["CH-649-CRF"],"award-info":[{"award-number":["CH-649-CRF"]}],"id":[{"id":"10.13039\/100024327","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Excessive fructose consumption is increasingly linked to obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease, yet its impact on brown adipocytes remains poorly defined. Here, we investigated how fructose alters brown adipogenesis with a focus on thyroid hormone receptor (THR) signaling. Differentiation of mouse brown preadipocytes in fructose-containing medium resulted in markedly reduced lipid droplet size and number, impaired expression of adipogenic markers (PPAR\u03b3, FABP4), and a loss of the brown adipocyte identity protein UCP-1. Whereas triiodothyronine (T3) and the THR\u03b2-selective agonist resmetirom dose-dependently enhanced UCP-1 expression in glucose medium, neither T3 nor resmetirom restored UCP-1 in fructose medium, revealing thyroid hormone resistance. Mechanistically, fructose specifically downregulated THR but not its heterodimer partner, retinoid X receptor (RXR), via ubiquitin-mediated degradation. Overexpression of THR rescued UCP-1 in glucose medium and promoted dynamic lipid turnover but failed to restore UCP-1 or lipid remodeling in fructose medium, indicating a defect in THR transcriptional regulation. Our secretome proteomics revealed that both the sugar source and THR overexpression strongly remodel the secreted protein landscape of brown adipocytes. The data indicate that fructose both reconfigures metabolic and signaling networks and blunts oxidative resilience, while excess THR activity in fructose conditions disrupts energy metabolism and increases the risk of protein misfolding. All these could contribute to THR dysfunction and impair adipogenesis. Collectively, these findings identify fructose as a potent inhibitor of brown adipogenesis, suppressing THR-dependent UCP-1 expression by inducing thyroid hormone resistance through a defect in THR-mediated transcriptional regulation. This mechanism links dietary fructose to impaired brown adipocytes and metabolic imbalance.<\/jats:p>","DOI":"10.1242\/bio.062648","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:27:57Z","timestamp":1780561677000},"source":"Crossref","is-referenced-by-count":0,"title":["Fructose impairs brown adipogenesis by promoting thyroid hormone resistance in differentiated brown adipocytes"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8739-9540","authenticated-orcid":false,"given":"Xiangdong","family":"Wu","sequence":"first","affiliation":[{"name":"University of Maryland School of Medicine 1 Department of Diagnostic Radiology & Nuclear Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salaheldeen","family":"Elsaid","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine 1 Department of Diagnostic Radiology & Nuclear Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Towson University 2 Department of Computer & Information Sciences , , Baltimore, MD 21252 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Rezyko LLC 3 , Seattle, WA 98109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junkai","family":"Hu","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine 1 Department of Diagnostic Radiology & Nuclear Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Yu","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine 4 Division of Endocrinology, Diabetes and Nutrition at the Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui Seng","family":"Tee","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine 1 Department of Diagnostic Radiology & Nuclear Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"2026062203300417400_BIO062648C1","doi-asserted-by":"publisher","first-page":"14078","DOI":"10.1074\/jbc.C110.107375","article-title":"Thyroid hormone regulates hepatic expression of fibroblast growth factor 21 in a PPAR\u03b1-dependent manner","volume":"285","author":"Adams","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2026062203300417400_BIO062648C2","doi-asserted-by":"publisher","first-page":"16251","DOI":"10.1073\/pnas.0508556102","article-title":"Thyroid hormone receptor \u03b2 mutants: Dominant negative regulators of peroxisome proliferator-activated receptor \u03b3 action","volume":"102","author":"Araki","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026062203300417400_BIO062648C3","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.1016\/j.bbagen.2012.07.001","article-title":"The in vivo role of nuclear receptor corepressors in thyroid hormone action","volume":"1830","author":"Astapova","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"2026062203300417400_BIO062648C4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1096\/fj.00-0502fje","article-title":"Triiodothyronine-mediated upregulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes","volume":"15","author":"Barbe","year":"2001","journal-title":"FASEB J."},{"key":"2026062203300417400_BIO062648C5","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.biocel.2011.12.021","article-title":"Diverse biological functions of the SPARC family of proteins","volume":"44","author":"Bradshaw","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2026062203300417400_BIO062648C6","doi-asserted-by":"publisher","first-page":"11268","DOI":"10.3390\/ijms231911268","article-title":"Resistance to thyroid hormones: a case-series study","volume":"23","author":"Cannarella","year":"2022","journal-title":"IJMS"},{"key":"2026062203300417400_BIO062648C7","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jinorgbio.2014.01.005","article-title":"Modulation of nuclear receptor function by cellular redox poise","volume":"133","author":"Carter","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"2026062203300417400_BIO062648C8","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.2337\/dc19-2494","article-title":"Fasting serum fructose levels are associated with risk of incident type 2 diabetes in middle-aged and older chinese population","volume":"43","author":"Chen","year":"2020","journal-title":"Diabetes Care"},{"key":"2026062203300417400_BIO062648C9","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1210\/er.2009-0007","article-title":"Molecular aspects of thyroid hormone actions","volume":"31","author":"Cheng","year":"2010","journal-title":"Endocr. Rev."},{"key":"2026062203300417400_BIO062648C10","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1056\/NEJMra2032804","article-title":"Reassessing human adipose tissue","volume":"386","author":"Cypess","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"2026062203300417400_BIO062648C11","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1038\/s41366-021-00902-6","article-title":"Non-hematopoietic IL-4R\u03b1 expression contributes to fructose-driven obesity and metabolic sequelae","volume":"45","author":"Damen","year":"2021","journal-title":"Int. J. Obes."},{"key":"2026062203300417400_BIO062648C12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/joim.13729","article-title":"Association between higher duodenal levels of the fructose carrier glucose transporter-5 and nonalcoholic fatty liver disease and liver fibrosis","volume":"295","author":"De Vito","year":"2024","journal-title":"J. Intern. Med."},{"key":"2026062203300417400_BIO062648C13","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.cmet.2019.10.001","article-title":"Proteomics-based comparative mapping of the secretomes of human brown and white adipocytes reveals EPDR1 as a novel batokine","volume":"30","author":"Deshmukh","year":"2019","journal-title":"Cell Metab."},{"key":"2026062203300417400_BIO062648C14","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1369\/jhc.2009.953190","article-title":"Ketohexokinase: expression and localization of the principal fructose-metabolizing enzyme","volume":"57","author":"Diggle","year":"2009","journal-title":"J. Histochem. Cytochem."},{"key":"2026062203300417400_BIO062648C15","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1002\/2211-5463.13846","article-title":"Fructose vs. glucose: modulating stem cell growth and function through sugar supplementation","volume":"14","author":"Elsaid","year":"2024","journal-title":"FEBS Open Bio"},{"key":"2026062203300417400_BIO062648C16","doi-asserted-by":"publisher","first-page":"E514","DOI":"10.1152\/ajpendo.90433.2008","article-title":"Thyroid-stimulating hormone receptor in brown adipose tissue is involved in the regulation of thermogenesis","volume":"295","author":"Endo","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2026062203300417400_BIO062648C17","doi-asserted-by":"publisher","first-page":"e1800070","DOI":"10.1101\/412692","article-title":"Large-scale analysis of redox-sensitive conditionally disordered protein regions reveals their widespread nature and key roles in high-level eukaryotic processes","volume":"19","author":"Erd\u0151s","year":"2018","journal-title":"Proteomics"},{"key":"2026062203300417400_BIO062648C18","doi-asserted-by":"publisher","first-page":"17462","DOI":"10.1073\/pnas.1107474108","article-title":"Resistance to thyroid hormone is modulated in vivo by the nuclear receptor corepressor (NCOR1)","volume":"108","author":"Fozzatti","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026062203300417400_BIO062648C19","doi-asserted-by":"publisher","first-page":"7850","DOI":"10.1073\/pnas.1222334110","article-title":"Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor \u03b1","volume":"110","author":"Fozzatti","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026062203300417400_BIO062648C20","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1089\/thy.2018.0399","article-title":"Genetic and pharmacological targeting of transcriptional repression in resistance to thyroid hormone alpha","volume":"29","author":"Freudenthal","year":"2019","journal-title":"Thyroid"},{"key":"2026062203300417400_BIO062648C21","doi-asserted-by":"publisher","first-page":"426","DOI":"10.3177\/jnsv.53.426","article-title":"Nutritional and hormonal regulation of uncoupling protein gene expression in rat adipocytes","volume":"53","author":"Fukuda","year":"2007","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"2026062203300417400_BIO062648C22","doi-asserted-by":"publisher","first-page":"e4415","DOI":"10.1097\/MD.0000000000004415","article-title":"Thyroid hormone resistance syndrome caused by heterozygous A317T mutation in thyroid hormone receptor \u03b2 gene: report of one Chinese pedigree and review of the literature","volume":"95","author":"Guo","year":"2016","journal-title":"Medicine"},{"key":"2026062203300417400_BIO062648C23","doi-asserted-by":"publisher","first-page":"4292","DOI":"10.1210\/en.2006-0116","article-title":"Mouse sterol response element binding protein-1c gene expression is negatively regulated by thyroid hormone","volume":"147","author":"Hashimoto","year":"2006","journal-title":"Endocrinology"},{"key":"2026062203300417400_BIO062648C24","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1055\/s-2004-821232","article-title":"Mutation analysis of leukemia inhibitory factor-receptor (LIF-R) in ACTH-secreting pituitary adenomas","volume":"112","author":"Heutling","year":"2004","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"2026062203300417400_BIO062648C25","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1476-511x-10-20","article-title":"Fructose impairs glucose-induced hepatic triglyceride synthesis","volume":"10","author":"Huang","year":"2011","journal-title":"Lipids Health Dis."},{"key":"2026062203300417400_BIO062648C26","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.bbamcr.2010.01.022","article-title":"Moonlighting proteins: an intriguing mode of multitasking","volume":"1803","author":"Huberts","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"2026062203300417400_BIO062648C27","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1515\/macvetrev-2016-0089","article-title":"Comparative study of glucose transporters GLUT-2 and GLUT-5 in ostriches gastrointestinal tract","volume":"39","author":"Hussar","year":"2016","journal-title":"Maced. Vet. Rev."},{"key":"2026062203300417400_BIO062648C28","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.jhep.2018.01.019","article-title":"Fructose and sugar: A major mediator of non-alcoholic fatty liver disease","volume":"68","author":"Jensen","year":"2018","journal-title":"J. Hepatol."},{"key":"2026062203300417400_BIO062648C29","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1002\/aur.1838","article-title":"Analysis and functional characterization of sequence variations in ligand binding domain of thyroid hormone receptors in autism spectrum disorder (ASD) patients","volume":"10","author":"Kalikiri","year":"2017","journal-title":"Autism Res."},{"key":"2026062203300417400_BIO062648C30","doi-asserted-by":"publisher","first-page":"E1736","DOI":"10.1152\/ajpendo.00122.2007","article-title":"PPAR\u03b3 regulates adipose triglyceride lipase in adipocytes in vitro and in vivo","volume":"293","author":"Kershaw","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2026062203300417400_BIO062648C31","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.bbalip.2014.03.013","article-title":"Physiological regulation of lipoprotein lipase","volume":"1841","author":"Kersten","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"2026062203300417400_BIO062648C32","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1097\/00054725-200307000-00002","article-title":"Expression of protease-activated receptor 2 in ulcerative colitis","volume":"9","author":"Kim","year":"2003","journal-title":"Inflamm. Bowel Dis."},{"key":"2026062203300417400_BIO062648C33","doi-asserted-by":"publisher","first-page":"447","DOI":"10.3803\/EnM.2020.920","article-title":"DEHP down-regulates Tshr gene expression in rat thyroid tissues and FRTL-5 Rat thyrocytes: a potential mechanism of thyroid disruption","volume":"36","author":"Kim","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"2026062203300417400_BIO062648C34","doi-asserted-by":"publisher","first-page":"15241","DOI":"10.3390\/ijms232315241","article-title":"Atrial fibrillation with heart failure in a case with resistance to thyroid hormone due to a rare thyroid hormone receptor \u03b2 gene mutation","volume":"23","author":"Lai","year":"2022","journal-title":"IJMS"},{"key":"2026062203300417400_BIO062648C35","doi-asserted-by":"publisher","first-page":"C463","DOI":"10.1152\/ajpcell.00010.2011","article-title":"Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes","volume":"302","author":"Lee","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2026062203300417400_BIO062648C36","doi-asserted-by":"publisher","first-page":"114516","DOI":"10.1101\/2023.10.30.564549","article-title":"Fatty acid synthesis promotes inflammasome activation through NLRP3 palmitoylation","volume":"43","author":"Leishman","year":"2023","journal-title":"Cell Rep."},{"key":"2026062203300417400_BIO062648C37","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1055\/s-2007-1010845","article-title":"Hepatic and adipose tissue lipogenesis as related to age and thyroid status in the rat","volume":"20","author":"Levacher","year":"1988","journal-title":"Horm. Metab. Res."},{"key":"2026062203300417400_BIO062648C38","doi-asserted-by":"publisher","first-page":"e36297","DOI":"10.1371\/journal.pone.0036297","article-title":"Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) \u03b3 activators and pan-PPAR partial agonists","volume":"7","author":"Liberato","year":"2012","journal-title":"PLoS ONE"},{"key":"2026062203300417400_BIO062648C39","doi-asserted-by":"publisher","first-page":"09603271231217992","DOI":"10.1177\/09603271231217992","article-title":"Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue","volume":"42","author":"Liu","year":"2023","journal-title":"Hum. Exp. Toxicol."},{"key":"2026062203300417400_BIO062648C40","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1089\/ars.2006.8.1419","article-title":"Zinc coordination environments in proteins as redox sensors and signal transducers","volume":"8","author":"Maret","year":"2006","journal-title":"Antioxid Redox Signal."},{"key":"2026062203300417400_BIO062648C41","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.1210\/jc.2003-031800","article-title":"Thyroid hormone and the adipocyte","volume":"88","author":"Mariash","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2026062203300417400_BIO062648C42","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1021\/ja0011616","article-title":"Reactivity of zinc finger cores: analysis of protein packing and electrostatic screening","volume":"123","author":"Maynard","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"2026062203300417400_BIO062648C43","doi-asserted-by":"publisher","first-page":"eabh3839","DOI":"10.1126\/scisignal.abh3839","article-title":"Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP","volume":"14","author":"Mendoza","year":"2021","journal-title":"Sci. Signal"},{"key":"2026062203300417400_BIO062648C44","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1074\/mcp.R500001-MCP200","article-title":"Coregulator interactions with the thyroid hormone receptor","volume":"4","author":"Moore","year":"2005","journal-title":"Mol. Cell. Proteomics"},{"key":"2026062203300417400_BIO062648C45","doi-asserted-by":"publisher","first-page":"e84569","DOI":"10.1371\/journal.pone.0084569","article-title":"Analysis of RXR\/THR and RXR\/PPARG2 heterodimerization by bioluminescence resonance energy transfer (BRET)","volume":"8","author":"Mulero","year":"2013","journal-title":"PLoS ONE"},{"key":"2026062203300417400_BIO062648C46","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1101\/gad.13.24.3209","article-title":"Mechanism of corepressor binding and release from nuclear hormone receptors","volume":"13","author":"Nagy","year":"1999","journal-title":"Genes Dev."},{"key":"2026062203300417400_BIO062648C47","doi-asserted-by":"publisher","first-page":"e12240","DOI":"10.1590\/1414-431x2022e12240","article-title":"Fructose consumption induces molecular adaptations involving thyroid function and thyroid-related genes in brown adipose tissue in rats","volume":"55","author":"Neto","year":"2022","journal-title":"Braz. J. Med. Biol. Res."},{"key":"2026062203300417400_BIO062648C48","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/nrm2617","article-title":"Mechanisms of regulated unconventional protein secretion","volume":"10","author":"Nickel","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026062203300417400_BIO062648C49","doi-asserted-by":"publisher","first-page":"e40876","DOI":"10.1371\/journal.pone.0040876","article-title":"Higher levels of ATGL are associated with exercise-induced enhancement of lipolysis in rat epididymal adipocytes","volume":"7","author":"Ogasawara","year":"2012","journal-title":"PLoS ONE"},{"key":"2026062203300417400_BIO062648C50","doi-asserted-by":"publisher","first-page":"10363","DOI":"10.1074\/jbc.274.15.10363","article-title":"Redox-dependent regulation of nuclear import of the glucocorticoid receptor","volume":"274","author":"Okamoto","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2026062203300417400_BIO062648C51","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3390\/ijms22010109","article-title":"Interplay between thyroid hormones and stearoyl-CoA desaturase 1 in the regulation of lipid metabolism in the heart","volume":"22","author":"Olichwier","year":"2020","journal-title":"IJMS"},{"key":"2026062203300417400_BIO062648C52","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nrendo.2014.143","article-title":"Thyroid hormone receptors and resistance to thyroid hormone disorders","volume":"10","author":"Ortiga-Carvalho","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"2026062203300417400_BIO062648C53","doi-asserted-by":"publisher","first-page":"83","DOI":"10.21203\/rs.3.rs-41498\/v1","article-title":"Dietary fructose and risk of metabolic syndrome in chinese residents aged 45 and above: results from the china national nutrition and health survey","volume":"20","author":"Pang","year":"2020","journal-title":"Nutr. J."},{"key":"2026062203300417400_BIO062648C54","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.molmet.2015.10.005","article-title":"Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis","volume":"5","author":"Razzoli","year":"2016","journal-title":"Mol. Metab."},{"key":"2026062203300417400_BIO062648C55","doi-asserted-by":"publisher","first-page":"913030","DOI":"10.3389\/fgene.2022.913030","article-title":"p53 regulates a miRNA-fructose transporter axis in brown adipose tissue under fasting","volume":"13","author":"Reinisch","year":"2022","journal-title":"Front. Genet."},{"key":"2026062203300417400_BIO062648C56","doi-asserted-by":"publisher","first-page":"6162","DOI":"10.3390\/ijms26136162","article-title":"Fructose-induced glycation end products promote skin-aging phenotypes and senescence marker expression in human dermal fibroblasts","volume":"26","author":"Rella","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"2026062203300417400_BIO062648C57","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1159\/000335812","article-title":"Complete activation of thyroid hormone receptor \u03b2 by T3 is essential for normal cochlear function and morphology in mice","volume":"28","author":"Richter","year":"2011","journal-title":"Cell. Physiol. Biochem."},{"key":"2026062203300417400_BIO062648C58","doi-asserted-by":"publisher","first-page":"14827","DOI":"10.1074\/jbc.M117.783043","article-title":"Coordinated transcriptional control of adipocyte triglyceride lipase (Atgl) by transcription factors Sp1 and peroxisome proliferator\u2013activated receptor \u03b3 (PPAR\u03b3) during adipocyte differentiation","volume":"292","author":"Roy","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2026062203300417400_BIO062648C59","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1530\/EC-20-0562","article-title":"Thyroid hormones in the regulation of brown adipose tissue thermogenesis","volume":"10","author":"Sentis","year":"2021","journal-title":"Endocr. Connect."},{"key":"2026062203300417400_BIO062648C60","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-1-4939-6820-6_8","article-title":"Protocols for generation of immortalized human brown and white preadipocyte cell lines","volume-title":"Thermogenic Fat","author":"Shamsi","year":"2017"},{"key":"2026062203300417400_BIO062648C80","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3390\/obesities4020010","article-title":"High-Fat-High-Fructose Diet Elicits Brown Adipocyte Dysfunction through miRNA-103 Induced miRNA Biogenesis Pathway","volume":"4","author":"Shree","year":"2024","journal-title":"Obesities"},{"key":"2026062203300417400_BIO062648C61","doi-asserted-by":"publisher","first-page":"293","DOI":"10.2337\/diabetes.51.2.293","article-title":"transcriptional regulation of adipocyte hormone-sensitive lipase by glucose","volume":"51","author":"Smih","year":"2002","journal-title":"Diabetes"},{"key":"2026062203300417400_BIO062648C62","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3109\/10408363.2015.1084990","article-title":"Sugar consumption, metabolic disease and obesity: the state of the controversy","volume":"53","author":"Stanhope","year":"2016","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"2026062203300417400_BIO062648C63","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4274\/jcrpe.v3i2.11","article-title":"Thyroid hormones and growth in health and disease - review","volume":"3","author":"Tar\u0131m","year":"2011","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"2026062203300417400_BIO062648C64","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1074\/jbc.M112.437970","article-title":"Role of Sirtuin 1 in the regulation of hepatic gene expression by thyroid hormone","volume":"288","author":"Thakran","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2026062203300417400_BIO062648C65","doi-asserted-by":"publisher","first-page":"217","DOI":"10.47119\/IJRP10013911220235792","article-title":"High fructose consumption increases liver GLUT-2 expression and the benefits of exercise on the liver metabolism: a literature review","volume":"139","author":"Trio Pamungkas","year":"2023","journal-title":"IJRP"},{"key":"2026062203300417400_BIO062648C66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.20935\/AcadBiol6069","article-title":"Does insulin resistance contribute to the \u2018unbrowning\u2019 of brown adipose tissue?","volume":"1","author":"Tulp","year":"2023","journal-title":"Academia Biol."},{"key":"2026062203300417400_BIO062648C67","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3389\/fphys.2019.00067","article-title":"Secretory proteome of brown adipocytes in response to cAMP-mediated thermogenic activation","volume":"10","author":"Villarroya","year":"2019","journal-title":"Front. Physiol."},{"key":"2026062203300417400_BIO062648C68","doi-asserted-by":"publisher","first-page":"4409","DOI":"10.1038\/s41467-023-40039-w","article-title":"Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice","volume":"14","author":"Wali","year":"2023","journal-title":"Nat. Commun."},{"key":"2026062203300417400_BIO062648C69","doi-asserted-by":"publisher","first-page":"848983","DOI":"10.3389\/fnut.2022.848983","article-title":"Maternal high-fructose intake activates myogenic program in fetal brown fat and predisposes offspring to diet-induced metabolic dysfunctions in adulthood","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Nutr."},{"key":"2026062203300417400_BIO062648C70","doi-asserted-by":"publisher","first-page":"8406","DOI":"10.1021\/bi000282f","article-title":"Preferential oxidation of zinc finger 2 in estrogen receptor dna-binding domain prevents dimerization and, hence, DNA binding","volume":"39","author":"Whittal","year":"2000","journal-title":"Biochemistry"},{"key":"2026062203300417400_BIO062648C71","doi-asserted-by":"publisher","first-page":"e70072","DOI":"10.1002\/cpz1.70072","article-title":"Establishing immortalized brown and white preadipocyte cell lines from young and aged mice","volume":"4","author":"Wu","year":"2024","journal-title":"Curr. Protocol."},{"key":"2026062203300417400_BIO062648C72","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1158\/0008-5472.CAN-23-2266","article-title":"PRMT1 Sustains De Novo fatty acid synthesis by methylating PHGDH to drive chemoresistance in triple-negative breast cancer","volume":"84","author":"Yamamoto","year":"2024","journal-title":"Cancer Res."},{"key":"2026062203300417400_BIO062648C73","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.isci.2019.10.002","article-title":"Revealing a mutant-induced receptor allosteric mechanism for the thyroid hormone resistance","volume":"20","author":"Yao","year":"2019","journal-title":"iScience"},{"key":"2026062203300417400_BIO062648C74","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1152\/physrev.2001.81.3.1097","article-title":"Physiological and molecular basis of thyroid hormone action","volume":"81","author":"Yen","year":"2001","journal-title":"Physiol. Rev."},{"key":"2026062203300417400_BIO062648C75","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1146\/annurev.physiol.62.1.439","article-title":"The mechanism of action of thyroid hormones","volume":"62","author":"Zhang","year":"2000","journal-title":"Annu. Rev. Physiol."},{"key":"2026062203300417400_BIO062648C76","doi-asserted-by":"publisher","first-page":"14458","DOI":"10.1021\/acs.analchem.9b03121","article-title":"Proteinase K combining two-step liquid\u2013liquid extraction for plasma untargeted liquid chromatography\u2013mass spectrometry-based metabolomics to discover the potential mechanism of colorectal adenoma","volume":"91","author":"Zhang","year":"2019","journal-title":"Anal. Chem."},{"key":"2026062203300417400_BIO062648C77","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1530\/JME-20-0250","article-title":"ACOX1, regulated by C\/EBP\u03b1 and miR-25-3p, promotes bovine preadipocyte adipogenesis","volume":"66","author":"Zhang","year":"2021","journal-title":"J. Mol. Endocrinol."},{"key":"2026062203300417400_BIO062648C81","doi-asserted-by":"publisher","first-page":"5299","DOI":"10.1113\/jp289263","article-title":"Revisiting brown adipose tissue whitening: Physiological mechanisms and pathophysiological consequences","volume":"603","author":"Zhao","year":"2025","journal-title":"The Journal of Physiology"},{"key":"2026062203300417400_BIO062648C78","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1097\/MED.0b013e32833d6d46","article-title":"New insights into regulation of lipid metabolism by thyroid hormone","volume":"17","author":"Zhu","year":"2010","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"2026062203300417400_BIO062648C79","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1055\/s-2003-40463","article-title":"Expression of thyroid hormone receptor isoform \u03b11 in pancreatic islets","volume":"111","author":"Zinke","year":"2003","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"2026062203300417400_BIO062648C82","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45803-x","article-title":"Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR","volume":"9","author":"Zwarts","year":"2019","journal-title":"Scientific Reports"}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062648\/3702208\/bio062648.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062648\/3705308\/bio062648.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062648\/3705308\/bio062648.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:30:17Z","timestamp":1782113417000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/15\/6\/bio062648\/372028\/Fructose-impairs-brown-adipogenesis-by-promoting"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":82,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.062648","relation":{},"ISSN":["2046-6390"],"issn-type":[{"value":"2046-6390","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]},"article-number":"bio062648"}}