Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis.

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dc.contributor.author Nie, Tao en
dc.contributor.author Hui, Xiaoyan en
dc.contributor.author Mao, Liufeng en
dc.contributor.author Nie, Baoming en
dc.contributor.author Li, Kuai en
dc.contributor.author Sun, Wei en
dc.contributor.author Gao, Xuefei en
dc.contributor.author Tang, Xiaofeng en
dc.contributor.author Xu, Yong en
dc.contributor.author Jiang, Baishan en
dc.contributor.author Tu, Zhengcao en
dc.contributor.author Li, Peng en
dc.contributor.author Ding, Ke en
dc.contributor.author Han, Weiping en
dc.contributor.author Zhang, Shaoping en
dc.contributor.author Xu, Aimin en
dc.contributor.author Ding, Sheng en
dc.contributor.author Liu, Pentao en
dc.contributor.author Patterson, Adam en
dc.contributor.author Cooper, Garth en
dc.contributor.author Wu, Donghai en
dc.date.accessioned 2018-11-28T22:07:56Z en
dc.date.issued 2016-11-02 en
dc.identifier.citation Scientific Reports 6:10 pages Article number 36382 2016 en
dc.identifier.issn 2045-2322 en
dc.identifier.uri http://hdl.handle.net/2292/44682 en
dc.description.abstract 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. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Scientific reports en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Cells, Cultured en
dc.subject Adipocytes en
dc.subject Animals en
dc.subject Mice en
dc.subject Harmine en
dc.subject rac1 GTP-Binding Protein en
dc.subject DNA Helicases en
dc.subject Neuropeptides en
dc.subject MAP Kinase Signaling System en
dc.subject Energy Metabolism en
dc.subject Thermogenesis en
dc.subject Adipocytes, Brown en
dc.subject Adipocytes, White en
dc.subject Diet, High-Fat en
dc.title Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis. en
dc.type Journal Article en
dc.identifier.doi 10.1038/srep36382 en
pubs.begin-page 36382 en
pubs.volume 6 en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 27805061 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 545863 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.org-id Science en
pubs.org-id Biological Sciences en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 2045-2322 en
pubs.record-created-at-source-date 2016-11-03 en
pubs.dimensions-id 27805061 en

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https://creativecommons.org/licenses/by/4.0/ Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/


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