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Article: Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis

TitleHarmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis
Authors
Issue Date2016
Citation
Scientific Reports, 2016, v. 6, p. 36382 How to Cite?
Abstract© The Author(s) 2016.Harmine is a natural compound possessing insulin-sensitizing effect in db/db diabetic mice. However its effect on adipose tissue browning is unknown. Here we reveal that harmine antagonizes high fat diet-induced adiposity. Harmine-treated mice gained less weight on a high fat diet and displayed increased energy expenditure and adipose tissue thermogenesis. In vitro, harmine potently induced the expression of thermogenic genes in both brown and white adipocytes, which was largely abolished by inhibition of RAC1/MEK/ERK pathway. Post-transcriptional modification analysis revealed that chromodomain helicase DNA binding protein 4 (CHD4) is a potential downstream target of harmine-mediated ERK activation. CHD4 directly binds the proximal promoter region of Ucp1, which is displaced upon treatment of harmine, thereby serving as a negative modulator of Ucp1. Thus, here we reveal a new application of harmine in combating obesity via this off-target effect in adipocytes.
Persistent Identifierhttp://hdl.handle.net/10722/238902
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNie, Tao-
dc.contributor.authorHui, Xiaoyan-
dc.contributor.authorMao, Liufeng-
dc.contributor.authorNie, Baoming-
dc.contributor.authorLi, Kuai-
dc.contributor.authorSun, Wei-
dc.contributor.authorGao, Xuefei-
dc.contributor.authorTang, Xiaofeng-
dc.contributor.authorXu, Yong-
dc.contributor.authorJiang, Baishan-
dc.contributor.authorTu, Zhengcao-
dc.contributor.authorLi, Peng-
dc.contributor.authorDing, Ke-
dc.contributor.authorHan, Weiping-
dc.contributor.authorZhang, Shaoping-
dc.contributor.authorXu, Aimin-
dc.contributor.authorDing, Sheng-
dc.contributor.authorLiu, Pentao-
dc.contributor.authorPatterson, Adam-
dc.contributor.authorCooper, Garth-
dc.contributor.authorWu, Donghai-
dc.date.accessioned2017-02-20T03:17:50Z-
dc.date.available2017-02-20T03:17:50Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, p. 36382-
dc.identifier.urihttp://hdl.handle.net/10722/238902-
dc.description.abstract© The Author(s) 2016.Harmine is a natural compound possessing insulin-sensitizing effect in db/db diabetic mice. However its effect on adipose tissue browning is unknown. Here we reveal that harmine antagonizes high fat diet-induced adiposity. Harmine-treated mice gained less weight on a high fat diet and displayed increased energy expenditure and adipose tissue thermogenesis. In vitro, harmine potently induced the expression of thermogenic genes in both brown and white adipocytes, which was largely abolished by inhibition of RAC1/MEK/ERK pathway. Post-transcriptional modification analysis revealed that chromodomain helicase DNA binding protein 4 (CHD4) is a potential downstream target of harmine-mediated ERK activation. CHD4 directly binds the proximal promoter region of Ucp1, which is displaced upon treatment of harmine, thereby serving as a negative modulator of Ucp1. Thus, here we reveal a new application of harmine in combating obesity via this off-target effect in adipocytes.-
dc.languageeng-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License-
dc.titleHarmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep36382-
dc.identifier.scopuseid_2-s2.0-84994247031-
dc.identifier.hkuros282742-
dc.identifier.volume6-
dc.identifier.spagenull-
dc.identifier.spage36382-
dc.identifier.epagenull-
dc.identifier.epage36382-
dc.identifier.eissn2045-2322-
dc.identifier.isiWOS:000386764900001-

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