{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:54:29Z","timestamp":1793130869861,"version":"4.5.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Obesity is a metabolic disease that is characterized by an excessive accumulation of adipose tissue (AT) and is often associated with other pathologies. AT is a lipid storage organ with endocrine functions that presents two main phenotypes: white adipose tissue (WAT) and brown adipose tissue (BAT). Preadipocytes or mature white adipocyte cells can differentiate in a middle phenotype with morpho\/functional characteristics between WAT and BAT, known as brown-like or beige adipose tissue (BeAT), through the browning process. Considering the interest in stimulating the browning process in metabolic disorders and the lack of clarity, evenness, and reproducibility of the preclinical models, the detailed description of an adipocyte differentiation protocol and the \u201c<jats:italic>de novo<\/jats:italic>\u201d development of a beige adipocyte phenotype has been described. Furthermore, the most described stimuli in inducing the browning process, such as PPAR-\u03b3 agonists (using rosiglitazone, RGZ) and \u03b2-adrenergic stimulators (using isoproterenol, ISO), were evaluated in order to describe their involvement in the browning process and identify a reference compound for the induction of the \u201c<jats:italic>de novo<\/jats:italic>\u201d browning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immortalized murine embryonic fibroblasts (3T3-L1) cells were differentiated for up to 17 days using a differentiation medium (DM) and a maintenance medium (MM) with or without RGZ or ISO to obtain both the mature white and the beige adipocyte phenotype. The differentiation was evaluated by the Oil Red O (ORO) staining assay, citrate synthase activity, and mitochondrial uncoupling protein 1 (UCP-1) immunodetection and expression performed on different days (T0, T3, T10, and T17) after the induction of differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results indicated that RGZ induced morphology and ORO-positive lipid deposits and increased the activity of citrate synthase enzyme and UCP-1 levels overlapping with a beige adipocyte phenotype after 17 days. ISO did not display a significant effect in these experimental conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, this work describes in depth the different phases of the adipocyte differentiation process by offering a detailed and reproducible \u201c<jats:italic>de novo<\/jats:italic>\u201d browning differentiation model. Furthermore, the efficacy of the stimulation of the PPAR-\u03b3 pathway in obtaining a beige adipocyte phenotype demonstrates that RGZ can induce the browning process and elects it as a perfect reference compound for experimental procedures in this field.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1546456","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T05:17:46Z","timestamp":1744607866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Development of an adipocyte differentiation protocol using 3T3-L1 cells for the investigation of the browning process: identification of the PPAR-\u03b3 agonist rosiglitazone as a browning reference drug"],"prefix":"10.3389","volume":"16","author":[{"given":"Lorenzo","family":"Flori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Galgani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Bray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ippolito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Segnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Pellegrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Citi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzia","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Martelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1292\/jvms.13-0359","article-title":"Induction of beige-like adipocytes in 3T3-L1 cells","volume":"76","author":"Asano","year":"2014","journal-title":"J. Veterinary Med. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nrendo.2013.204","article-title":"Adipose tissue browning and metabolic health","volume":"10","author":"Bartelt","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s11154-021-09690-w","article-title":"ATP-consuming futile cycles as energy dissipating mechanisms to counteract obesity","volume":"23","author":"Brownstein","year":"2022","journal-title":"Rev. Endocr. Metabolic Disord."},{"key":"B4","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1152\/physrev.00015.2003","article-title":"Brown adipose tissue: function and physiological significance","volume":"84","author":"Cannon","year":"2004","journal-title":"Physiol. Rev."},{"key":"B5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-1-4939-8994-2_25","article-title":"The use of 3T3-L1 murine preadipocytes as a model of adipogenesis","volume-title":"Pre-clinical models: techniques and protocols","author":"Cave","year":"2019"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.3390\/cells9041024","article-title":"E2F1 regulates adipocyte differentiation and adipogenesis by activating ICAT","volume":"9","author":"Chen","year":"2020","journal-title":"Cells"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1002\/ptr.6892","article-title":"Trigonelline induces browning in 3T3\u2010L1 white adipocytes","volume":"35","author":"Choi","year":"2021","journal-title":"Phytotherapy Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s42255-018-0021-8","article-title":"Metabolic adaptation and maladaptation in adipose tissue","volume":"1","author":"Chouchani","year":"2019","journal-title":"Nat. Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1172\/JCI88883","article-title":"The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis","volume":"127","author":"Crewe","year":"2017","journal-title":"J. Clin. investigation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/nature05488","article-title":"Abdominal obesity and metabolic syndrome","volume":"444","author":"Despr\u00e9s","year":"2006","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6232","DOI":"10.1021\/acs.jafc.9b02191","article-title":"Combination of capsaicin and capsiate induces browning in 3T3-L1 white adipocytes via activation of the peroxisome proliferator-activated receptor \u03b3\/\u03b23-adrenergic receptor signaling pathways","volume":"67","author":"Fan","year":"2019","journal-title":"J. Agric. food Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1093\/ajcn\/nqy162","article-title":"Adipose tissue and skeletal muscle insulin-mediated glucose uptake in insulin resistance: role of blood flow and diabetes","volume":"108","author":"Ferrannini","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e145207","DOI":"10.1172\/jci.insight.145207","article-title":"Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade","volume":"6","author":"Ferrere","year":"2021","journal-title":"JCI insight"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1172\/JCI134892","article-title":"The \u03b23-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans","volume":"130","author":"Finlin","year":"2020","journal-title":"J. Clin. investigation"},{"key":"B15","doi-asserted-by":"publisher","first-page":"9276","DOI":"10.3390\/ijms24119276","article-title":"Influence of polyphenols on adipose tissue: sirtuins as pivotal players in the Browning process","volume":"24","author":"Flori","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1007\/s10753-014-9914-1","article-title":"Adipose tissue immune response: novel triggers and consequences for chronic inflammatory conditions","volume":"37","author":"Ghigliotti","year":"2014","journal-title":"Inflammation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"E350","DOI":"10.1152\/ajpendo.00387.2005","article-title":"UCP1 is essential for adaptive adrenergic nonshivering thermogenesis","volume":"291","author":"Golozoubova","year":"2006","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B18","doi-asserted-by":"publisher","first-page":"E608","DOI":"10.1152\/ajpendo.00009.2005","article-title":"Metabolic and cellular plasticity in white adipose tissue I: effects of beta3-adrenergic receptor activation","volume":"289","author":"Granneman","year":"2005","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B19","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.celrep.2019.03.026","article-title":"Mature human white adipocytes cultured under membranes maintain identity, function, and can transdifferentiate into brown-like adipocytes","volume":"27","author":"Harms","year":"2019","journal-title":"Cell Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/j.bbalip.2015.02.003","article-title":"Role of developmental transcription factors in white, brown and beige adipose tissues","volume":"1851","author":"Hilton","year":"2015","journal-title":"Biochimica Biophysica Acta (BBA)-Molecular Cell Biol. Lipids"},{"key":"B21","doi-asserted-by":"publisher","first-page":"C670","DOI":"10.1152\/ajpcell.2000.279.3.C670","article-title":"Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes","volume":"279","author":"Himms-Hagen","year":"2000","journal-title":"Am. J. Physiology-Cell Physiology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"20370","DOI":"10.1038\/s41598-024-71591-0","article-title":"Triiodothyronine (T3) promotes browning of white adipose through inhibition of the PI3K\/AKT signalling pathway","volume":"14","author":"Huang","year":"2024","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"498","DOI":"10.3389\/fendo.2020.00498","article-title":"UCP1 dependent and independent thermogenesis in brown and beige adipocytes","volume":"11","author":"Ikeda","year":"2020","journal-title":"Front. Endocrinol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"102977","DOI":"10.1016\/j.xpro.2024.102977","article-title":"Qualitative and quantitative analysis of lipid droplets in mature 3T3-L1 adipocytes using oil red O","volume":"5","author":"Kaczmarek","year":"2024","journal-title":"Star. Protoc."},{"key":"B27","doi-asserted-by":"publisher","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am. J. Physiology-Cell Physiology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.molmet.2015.04.006","article-title":"Genetic disruption of uncoupling protein 1 in mice renders brown adipose tissue a significant source of FGF21 secretion","volume":"4","author":"Keipert","year":"2015","journal-title":"Mol. Metab."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1210\/jc.2004-0395","article-title":"Adipose tissue as an endocrine organ","volume":"89","author":"Kershaw","year":"2004","journal-title":"J. Clin. Endocrinol. and Metabolism"},{"key":"B30","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3390\/nu12020427","article-title":"Ginsenoside Rg3 induces browning of 3T3-L1 adipocytes by activating AMPK signaling","volume":"12","author":"Kim","year":"2020","journal-title":"Nutrients"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.3390\/ph16121727","article-title":"Betanin from beetroot (beta vulgaris L.) regulates lipid metabolism and promotes fat browning in 3T3-L1 adipocytes","volume":"16","author":"Lee","year":"","journal-title":"Pharmaceuticals"},{"key":"B32","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s12272-023-01432-7","article-title":"Naringin promotes fat browning mediated by UCP1 activation via the AMPK signaling pathway in 3T3-L1 adipocytes","volume":"46","author":"Lee","year":"","journal-title":"Archives Pharmacal Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/j.1463-1326.2009.01149.x","article-title":"Selective effects of PPARgamma agonists and antagonists on human pre-adipocyte differentiation","volume":"12","author":"Leyvraz","year":"2010","journal-title":"Diabetes, Obes. Metabolism"},{"key":"B34","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nprot.2012.013","article-title":"Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice","volume":"7","author":"Lim","year":"2012","journal-title":"Nat. Protoc."},{"key":"B35","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/366740a0","article-title":"Development of obesity in transgenic mice after genetic ablation of brown adipose tissue","volume":"366","author":"Lowell","year":"1993","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12986-022-00694-0","article-title":"Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases","volume":"19","author":"Machado","year":"2022","journal-title":"Nutr. and metabolism"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.2174\/1871530323666230309144825","article-title":"Metabolic syndrome: the constellation of co-morbidities, a global threat","volume":"23","author":"Madan","year":"2023","journal-title":"Endocr. Metabolic and Immune Disorders-Drug Targets Formerly Curr. Drug Targets-Immune, Endocr. and Metabolic Disord."},{"key":"B38","doi-asserted-by":"publisher","first-page":"217","DOI":"10.4161\/adip.24953","article-title":"Adipose tissue depot and cell size dependency of adiponectin synthesis and secretion in human obesity","volume":"2","author":"Meyer","year":"2013","journal-title":"Adipocyte"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e0138344","DOI":"10.1371\/journal.pone.0138344","article-title":"Isoproterenol increases uncoupling, glycolysis, and markers of beiging in mature 3T3-L1 adipocytes","volume":"10","author":"Miller","year":"2015","journal-title":"PloS one"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/sj.ijo.0800770","article-title":"Adipose tissue as an endocrine and paracrine organ","volume":"22","author":"Mohamed-Ali","year":"1998","journal-title":"Int. J. Obes."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.3390\/cells10051126","article-title":"SIRT5 inhibition induces brown fat-like phenotype in 3T3-L1 preadipocytes","volume":"10","author":"Molinari","year":"2021","journal-title":"Cells"},{"key":"B42","doi-asserted-by":"publisher","first-page":"289645","DOI":"10.1155\/2010\/289645","article-title":"Chronic inflammation in obesity and the metabolic syndrome","volume":"2010","author":"Monteiro","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"B43","doi-asserted-by":"publisher","first-page":"11512","DOI":"10.3390\/ijms222111512","article-title":"Exercise-mediated browning of white adipose tissue: its significance, mechanism and effectiveness","volume":"22","author":"Mu","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/ijms18051006","article-title":"Inflammation downregulates UCP1 expression in brown adipocytes potentially via SIRT1 and DBC1 interaction","volume":"18","author":"N\u00f8hr","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4794780","DOI":"10.1155\/2020\/4794780","article-title":"Tyrosol may prevent obesity by inhibiting adipogenesis in 3T3\u2010L1 preadipocytes","volume":"2020","author":"Pacifici","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B46","doi-asserted-by":"publisher","first-page":"599134","DOI":"10.3389\/fendo.2021.599134","article-title":"Beige adipose tissue identification and marker Specificity\u2014overview","volume":"12","author":"Pilkington","year":"2021","journal-title":"Front. Endocrinol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3389\/fendo.2011.00087","article-title":"Differentiation of human adipose-derived stem cells into \u201cbrite\u201d(brown-in-white) adipocytes","volume":"2","author":"Pisani","year":"2011","journal-title":"Front. Endocrinol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1053\/beem.2002.0222","article-title":"Adipose tissue as an endocrine organ","volume":"16","author":"Prins","year":"2002","journal-title":"Best Pract. and Res. Clin. Endocrinol. and Metabolism"},{"key":"B49","doi-asserted-by":"publisher","first-page":"7833","DOI":"10.1073\/pnas.0802063105","article-title":"Cidea is associated with lipid droplets and insulin sensitivity in humans","volume":"105","author":"Puri","year":"2008","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"346","DOI":"10.3390\/ph16030346","article-title":"Anti-inflammatory, antioxidant, and WAT\/BAT-Conversion stimulation induced by novel PPAR ligands: results from ex vivo and in vitro studies","volume":"16","author":"Recinella","year":"2023","journal-title":"Pharmaceuticals"},{"key":"B51","doi-asserted-by":"publisher","first-page":"E344","DOI":"10.1152\/ajpendo.00418.2016","article-title":"CNS \u03b23-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight","volume":"313","author":"Richard","year":"2017","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2400","DOI":"10.1016\/S0140-6736(14)61744-X","article-title":"Patchy progress on obesity prevention: emerging examples, entrenched barriers, and new thinking","volume":"385","author":"Roberto","year":"2015","journal-title":"Lancet"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1002\/oby.21134","article-title":"Diet\u2010induced obesity causes insulin resistance in mouse brown adipose tissue","volume":"23","author":"Roberts\u2010Toler","year":"2015","journal-title":"Obesity"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1007\/s11154-023-09827-z","article-title":"White adipose tissue mitochondrial bioenergetics in metabolic diseases","volume":"24","author":"Sabaratnam","year":"2023","journal-title":"Rev. Endocr. Metabolic Disord."},{"key":"B55","doi-asserted-by":"publisher","first-page":"E676","DOI":"10.1152\/ajpendo.00028.2015","article-title":"Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice","volume":"310","author":"Sakamoto","year":"2016","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B56","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/s41574-019-0230-6","article-title":"The endocrine function of adipose tissues in health and cardiometabolic disease","volume":"15","author":"Scheja","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1101\/gad.1779209","article-title":"Transcriptional control of brown adipocyte development and physiological function\u2014of mice and men","volume":"23","author":"Seale","year":"2009","journal-title":"Genes and Dev."},{"key":"B58","doi-asserted-by":"publisher","first-page":"712","DOI":"10.3390\/nu10060712","article-title":"Spirulina maxima extract reduces obesity through suppression of adipogenesis and activation of browning in 3T3-L1 cells and high-fat diet-induced obese mice","volume":"10","author":"Seo","year":"2018","journal-title":"Nutrients"},{"key":"B59","doi-asserted-by":"publisher","first-page":"352","DOI":"10.2741\/s156","article-title":"Physiological importance and control of non-shivering facultative thermogenesis","volume":"3","author":"Silva","year":"2011","journal-title":"Front. Biosci. Sch. Ed."},{"key":"B60","doi-asserted-by":"publisher","first-page":"228","DOI":"10.23736\/S0391-1977.20.03192-2","article-title":"The possible role of endocrine dysfunction of adipose tissue in gestational diabetes mellitus","volume":"45","author":"\u0160imj\u00e1k","year":"2020","journal-title":"Minerva Endocrinol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1172\/JCI62308","article-title":"Brown adipose tissue regulates glucose homeostasis and insulin sensitivity","volume":"123","author":"Stanford","year":"2012","journal-title":"J. Clin. investigation"},{"key":"B62","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.coph.2017.08.006","article-title":"Adipose tissue inflammation in obesity: a metabolic or immune response?","volume":"37","author":"Stolarczyk","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.toxlet.2023.07.003","article-title":"Gadolinium-based contrast agents suppress adipocyte differentiation in 3T3-L1 cells","volume":"383","author":"Takanezawa","year":"2023","journal-title":"Toxicol. Lett."},{"key":"B64","doi-asserted-by":"publisher","first-page":"31894","DOI":"10.1074\/jbc.M606114200","article-title":"UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-\/-mice","volume":"281","author":"Ukropec","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B65","doi-asserted-by":"publisher","first-page":"e12997","DOI":"10.1111\/eci.12997","article-title":"Adipokine dysregulation and adipose tissue inflammation in human obesity","volume":"48","author":"Unamuno","year":"2018","journal-title":"Eur. J. Clin. investigation"},{"key":"B66","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1111\/joim.12803","article-title":"Inflammation of brown\/beige adipose tissues in obesity and metabolic disease","volume":"284","author":"Villarroya","year":"2018","journal-title":"J. Intern. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.1172\/JCI129191","article-title":"Contribution of adipogenesis to healthy adipose tissue expansion in obesity","volume":"129","author":"Vishvanath","year":"2019","journal-title":"J. Clin. investigation"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e13724","DOI":"10.1111\/obr.13724","article-title":"Inflammation\u2010mediated metabolic regulation in adipose tissue","volume":"25","author":"Xu","year":"2024","journal-title":"Obes. Rev."},{"key":"B69","first-page":"1616","article-title":"The related metabolic diseases and treatments of obesity","volume-title":"Healthcare (Basel)","author":"Yang","year":"2022"},{"key":"B70","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ab.2012.03.005","article-title":"Protocol for effective differentiation of 3T3-L1 cells to adipocytes","volume":"425","author":"Zebisch","year":"2012","journal-title":"Anal. Biochem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e0264772","DOI":"10.1371\/journal.pone.0264772","article-title":"Cistanche promotes the adipogenesis of 3T3-L1 preadipocytes","volume":"17","author":"Zhang","year":"2022","journal-title":"Plos one"},{"key":"B72","doi-asserted-by":"publisher","first-page":"155113","DOI":"10.1016\/j.phymed.2023.155113","article-title":"Hydroxy-\u03b1-sanshool from the fruits of Zanthoxylum bungeanum Maxim. promotes browning of white fat by activating TRPV1 to induce PPAR-\u03b3 deacetylation","volume":"121","author":"Zhang","year":"2023","journal-title":"Phytomedicine Int. J. phytotherapy Phytopharm."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1114767","DOI":"10.3389\/fendo.2023.1114767","article-title":"An insight into brown\/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin","volume":"14","author":"Ziqubu","year":"2023","journal-title":"Front. Endocrinol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.cmet.2017.12.002","article-title":"Anatomical, physiological, and functional diversity of adipose tissue","volume":"27","author":"Zwick","year":"2018","journal-title":"Cell metab."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1546456\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T05:17:47Z","timestamp":1744607867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1546456\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":74,"alternative-id":["10.3389\/fphar.2025.1546456"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1546456","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]},"article-number":"1546456"}}