{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:41:07Z","timestamp":1787701267299,"version":"build-2784847793"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rohto Pharmaceutical Co., Ltd.","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Various natural products (NPs) have been used to treat obesity and related diseases. However, the best way to fight obesity is preventive, with accurate body weight management through exercise, diet, or bioactive NPs to avoid obesity development. We demonstrated that green tea extract (GTE) is an anti-obesity NP using a zebrafish obesity model. Based on a hypothesis that GTE can prevent obesity, the objective of this study was to assess GTE\u2019s ability to attenuate obesity development. Juvenile zebrafish were pretreated with GTE for seven days before obesity induction via a high-fat diet; adult zebrafish were pretreated with GTE for two weeks before obesity induction by overfeeding. As a preventive intervention, GTE significantly decreased visceral adipose tissue accumulation in juveniles and ameliorated visceral adiposity and plasma triglyceride levels in adult zebrafish obesity models. RNA sequencing analysis was performed using liver tissues from adult obese zebrafish, with or without GTE administration, to investigate the underlying molecular mechanism. Transcriptome analysis revealed that preventive GTE treatment affects several pathways associated with anti-obesity regulation, including activation of STAT and downregulation of CEBP signaling pathways. In conclusion, GTE could be used as a preventive agent against obesity.<\/jats:p>","DOI":"10.3390\/molecules26092627","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T05:10:55Z","timestamp":1619759455000},"page":"2627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Preventive Effects of Green Tea Extract against Obesity Development in Zebrafish"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6936-795X","authenticated-orcid":false,"given":"Liqing","family":"Zang","sequence":"first","affiliation":[{"name":"Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie 514-8507, Japan"},{"name":"Zebrafish Drug Screening Center, Mie University, Tsu, Mie 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4111-8262","authenticated-orcid":false,"given":"Yasuhito","family":"Shimada","sequence":"additional","affiliation":[{"name":"Zebrafish Drug Screening Center, Mie University, Tsu, Mie 514-8507, Japan"},{"name":"Department of Integrative Pharmacology, Graduate School of Medicine, Mie University, Tsu, Mie 514-8507, Japan"},{"name":"Department of Bioinformatics, Advanced Science Research Promotion Center, Mie University, Tsu, Mie 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7335-6428","authenticated-orcid":false,"given":"Hiroko","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie 514-8507, Japan"},{"name":"Zebrafish Drug Screening Center, Mie University, Tsu, Mie 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Katsuzaki","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu, Mie 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngil","family":"Kim","sequence":"additional","affiliation":[{"name":"Rohto Pharmaceutical Co., Ltd., Osaka 530-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djong-Chi","family":"Chu","sequence":"additional","affiliation":[{"name":"Rohto Pharmaceutical Co., Ltd., Osaka 530-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lekh Raj","family":"Juneja","sequence":"additional","affiliation":[{"name":"Rohto Pharmaceutical Co., Ltd., Osaka 530-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Kuroyanagi","sequence":"additional","affiliation":[{"name":"UMOU Science Lab, Matsusaka, Mie 515-0303, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-4013","authenticated-orcid":false,"given":"Norihiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie 514-8507, Japan"},{"name":"Zebrafish Drug Screening Center, Mie University, Tsu, Mie 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020, June 11). Obesity and Overweight. Available online: https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/01.med.0000433068.09294.a1","article-title":"Obesity IS a disease!","volume":"20","author":"Apovian","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9571","DOI":"10.1021\/acs.jafc.6b04468","article-title":"Natural Products with Anti-obesity Effects and Different Mechanisms of Action","volume":"64","author":"Fu","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1038\/srep03708","article-title":"Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis","volume":"4","author":"Hiramitsu","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nakayama, H., Shimada, Y., Zang, L., Terasawa, M., Nishiura, K., Matsuda, K., Toombs, C., Langdon, C., and Nishimura, N. (2018). Novel Anti-Obesity Properties of Palmaria mollis in Zebrafish and Mouse Models. Nutrients, 10.","DOI":"10.3390\/nu10101401"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1021\/jf0628025","article-title":"Weight gain reduction in mice fed Panax ginseng saponin, a pancreatic lipase inhibitor","volume":"55","author":"Karu","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"674","DOI":"10.5551\/jat.1313","article-title":"Anti-obesity effect of fish oil and fish oil-fenofibrate combination in female KK mice","volume":"16","author":"Arai","year":"2009","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_8","first-page":"2185","article-title":"Obesity: Assessment and management in primary care","volume":"63","author":"Lyznicki","year":"2001","journal-title":"Am. Fam. Physician"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11548-010-0492-x","article-title":"Regional image analysis of the tongue color spectrum","volume":"6","author":"Yamamoto","year":"2011","journal-title":"Int. J. Comput. Assist. Radiol. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1023\/B:DDAS.0000020490.34220.6d","article-title":"Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats","volume":"49","author":"Park","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fnut.2018.00126","article-title":"Herbal Medicine Ninjin\u2019yoeito in the Treatment of Sarcopenia and Frailty","volume":"5","author":"Uto","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9129134","DOI":"10.1155\/2020\/9129134","article-title":"Suppression of Dynamical Network Biomarker Signals at the Predisease State (Mibyou) before Metabolic Syndrome in Mice by a Traditional Japanese Medicine (Kampo Formula) Bofutsushosan","volume":"2020","author":"Koizumi","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.foodchem.2005.03.015","article-title":"Extraction of active ingredients from green tea (Camellia sinensis): Extraction efficiency of major catechins and caffeine","volume":"96","author":"Knez","year":"2006","journal-title":"Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Prasanth, M.I., Sivamaruthi, B.S., Chaiyasut, C., and Tencomnao, T. (2019). A Review of the Role of Green Tea (Camellia sinensis) in Antiphotoaging, Stress Resistance, Neuroprotection, and Autophagy. Nutrients, 11.","DOI":"10.3390\/nu11020474"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.14694\/EdBook_AM.2013.33.92","article-title":"Green tea polyphenols and cancer chemoprevention of genitourinary cancer","volume":"33","author":"Bailey","year":"2013","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1207\/s15327914nc4701_2","article-title":"Tea Beverage in Chemoprevention of Prostate Cancer: A Mini-Review","volume":"47","author":"Saleem","year":"2003","journal-title":"Nutr. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, C.S., and Wang, H. (2016). Cancer Preventive Activities of Tea Catechins. Molecules, 21.","DOI":"10.3390\/molecules21121679"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.3390\/nu7075230","article-title":"Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome","volume":"7","author":"Legeay","year":"2015","journal-title":"Nutrients"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.phytochem.2008.11.011","article-title":"The potential role of green tea catechins in the prevention of the metabolic syndrome\u2014A review","volume":"70","author":"Thielecke","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Suzuki, T., Pervin, M., Goto, S., Isemura, M., and Nakamura, Y. (2016). Beneficial Effects of Tea and the Green Tea Catechin Epigallocatechin-3-gallate on Obesity. Molecules, 21.","DOI":"10.3390\/molecules21101305"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kaihatsu, K., Yamabe, M., and Ebara, Y. (2018). Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters. Molecules, 23.","DOI":"10.3390\/molecules23102475"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Furushima, D., Ide, K., and Yamada, H. (2018). Effect of Tea Catechins on Influenza Infection and the Common Cold with a Focus on Epidemiological\/Clinical Studies. Molecules, 23.","DOI":"10.3390\/molecules23071795"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1080\/10408399709527802","article-title":"Tea flavonoids and cardiovascular diseases: A review","volume":"37","author":"Tijburg","year":"1997","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pervin, M., Unno, K., Ohishi, T., Tanabe, H., Miyoshi, N., and Nakamura, Y. (2018). Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases. Molecules, 23.","DOI":"10.3390\/molecules23061297"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zang, L., Shimada, Y., Nakayama, H., Kim, Y., Chu, D.-C., Juneja, L.R., Kuroyanagi, J., and Nishimura, N. (2019). RNA-seq Based Transcriptome Analysis of the Anti-Obesity Effect of Green Tea Extract Using Zebrafish Obesity Models. Molecules, 24.","DOI":"10.3390\/molecules24183256"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1248\/jhs.51.161","article-title":"Tea Catechins with a Galloyl Moiety Reduce Body Weight and Fat","volume":"51","author":"Kajimoto","year":"2005","journal-title":"J. Health Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1038\/oby.2007.176","article-title":"A Green Tea Extract High in Catechins Reduces Body Fat and Cardiovascular Risks in Humans","volume":"15","author":"Nagao","year":"2007","journal-title":"Obesity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.physbeh.2007.10.009","article-title":"Effectiveness of green tea on weight reduction in obese Thais: A randomized, controlled trial","volume":"93","author":"Auvichayapat","year":"2008","journal-title":"Physiol. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1194\/jlr.D017012","article-title":"Zebrafish obesogenic test: A tool for screening molecules that target adiposity","volume":"52","author":"Ouadah","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Khan, N., and Mukhtar, H. (2018). Tea Polyphenols in Promotion of Human Health. Nutrients, 11.","DOI":"10.3390\/nu11010039"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Saeki, K., Hayakawa, S., Nakano, S., Ito, S., Oishi, Y., Suzuki, Y., and Isemura, M. (2018). In Vitro and In Silico Studies of the Molecular Interactions of Epigallocatechin-3-O-gallate (EGCG) with Proteins That Explain the Health Benefits of Green Tea. Molecules, 23.","DOI":"10.3390\/molecules23061295"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, X.-Q., Hu, T., Han, Y., Huang, W., Yuan, H.-B., Zhang, Y.-T., Du, Y., and Jiang, Y.-W. (2016). Preventive Effects of Catechins on Cardiovascular Disease. Molecules, 21.","DOI":"10.3390\/molecules21121759"},{"key":"ref_34","first-page":"180","article-title":"Blood brain barrier permeability of (\u2212)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice","volume":"9","author":"Pervin","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0092-8674(01)00240-9","article-title":"Obesity and the Regulation of Energy Balance","volume":"104","author":"Spiegelman","year":"2001","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nm.2627","article-title":"The cellular and signaling networks linking the immune system and metabolism in disease","volume":"18","author":"Osborn","year":"2012","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1038\/sj.onc.1210010","article-title":"UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas","volume":"26","author":"Berlingieri","year":"2007","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.1365-2559.2009.03296.x","article-title":"UbcH10 expression in human lymphomas","volume":"54","author":"Troncone","year":"2009","journal-title":"Histopathology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fonc.2013.00004","article-title":"Re-thinking cell cycle regulators: The cross-talk with metabolism","volume":"3","author":"Fajas","year":"2013","journal-title":"Front. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.tem.2011.03.007","article-title":"Emerging roles of JAK\u2013STAT signaling pathways in adipocytes","volume":"22","author":"Richard","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1111\/febs.13709","article-title":"The JAK\/STAT pathway in obesity and diabetes","volume":"283","author":"Gurzov","year":"2016","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1210\/en.2007-1148","article-title":"Adipose-specific disruption of signal transducer and activator of transcription 3 increases body weight and adiposity","volume":"149","author":"Cernkovich","year":"2008","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/hep.20400","article-title":"Interleukin 6 alleviates hepatic steatosis and ischemia\/reperfusion injury in mice with fatty liver disease","volume":"40","author":"Hong","year":"2004","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/hep.23837","article-title":"Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3","volume":"52","author":"Ki","year":"2010","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.tem.2008.11.005","article-title":"New developments in adipogenesis","volume":"20","author":"Lefterova","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Moseti, D., Regassa, A., and Kim, W.-K. (2016). Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010124"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103558","DOI":"10.1016\/j.jff.2019.103558","article-title":"Effects of (+)-catechin on the differentiation and lipid metabolism of 3T3-L1 adipocytes","volume":"62","author":"Jiang","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2013.09.001","article-title":"Novel insights of dietary polyphenols and obesity","volume":"25","author":"Wang","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5695","DOI":"10.1021\/jf050045p","article-title":"The Apoptotic Effect of Green Tea (\u2212)-Epigallocatechin Gallate on 3T3-L1 Preadipocytes Depends on the Cdk2 Pathway","volume":"53","author":"Wu","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1089\/zeb.2011.0726","article-title":"A Novel Protocol for the Oral Administration of Test Chemicals to Adult Zebrafish","volume":"8","author":"Zang","year":"2011","journal-title":"Zebrafish"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Oka, T., Nishimura, Y., Zang, L., Hirano, M., Shimada, Y., Wang, Z., Umemoto, N., Kuroyanagi, J., Nishimura, N., and Tanaka, T. (2010). Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity. BMC Physiol., 10.","DOI":"10.1186\/1472-6793-10-21"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1089\/zeb.2012.0862","article-title":"A Novel, Reliable Method for Repeated Blood Collection from Aquarium Fish","volume":"10","author":"Zang","year":"2013","journal-title":"Zebrafish"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zang, L., Shimada, Y., Nishimura, Y., Tanaka, T., and Nishimura, N. (2015). Repeated Blood Collection for Blood Tests in Adult Zebrafish. J. Vis. Exp., e53272.","DOI":"10.3791\/53272-v"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Peterson, S.M., and Freeman, J.L. (2009). RNA Isolation from Embryonic Zebrafish and cDNA Synthesis for Gene Expression Analysis. J. Vis. Exp., e1470.","DOI":"10.3791\/1470-v"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bullard, J.H., Purdom, E., Hansen, K.D., and Dudoit, S. (2010). Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-94"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2174\/1570163054064701","article-title":"New Approaches to Mechanism Analysis for Drug Discovery Using DNA Microarray Data Combined with KeyMolnet","volume":"2","author":"Sato","year":"2005","journal-title":"Curr. Drug Discov. Technol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/9\/2627\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:55:57Z","timestamp":1760162157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/9\/2627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,30]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["molecules26092627"],"URL":"https:\/\/doi.org\/10.3390\/molecules26092627","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,30]]}}}