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https://doi.org/10.1038/srep36382
Title: | Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis | Authors: | Nie, T Hui, X Mao, L Nie, B Li, K Sun, W Gao, X Tang, X Xu, Y Jiang, B Tu, Z Li, P Ding, K Han, W Zhang, S Xu, A Ding, S Liu, P Patterson, A Cooper, G Wu, D |
Keywords: | DNA helicase harmine Mi-2beta protein, mouse neuropeptide Rac1 protein Rac1 protein, mouse adipocyte animal brown adipocyte cell culture cytology drug effect energy metabolism genetics lipid diet MAPK signaling metabolism mouse thermogenesis white adipocyte Adipocytes Adipocytes, Brown Adipocytes, White Animals Cells, Cultured Diet, High-Fat DNA Helicases Energy Metabolism Harmine MAP Kinase Signaling System Mice Neuropeptides rac1 GTP-Binding Protein Thermogenesis |
Issue Date: | 2016 | Publisher: | Nature Publishing Group | Citation: | Nie, T, Hui, X, Mao, L, Nie, B, Li, K, Sun, W, Gao, X, Tang, X, Xu, Y, Jiang, B, Tu, Z, Li, P, Ding, K, Han, W, Zhang, S, Xu, A, Ding, S, Liu, P, Patterson, A, Cooper, G, Wu, D (2016). Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis. Scientific Reports 6 : 36382. ScholarBank@NUS Repository. https://doi.org/10.1038/srep36382 | Rights: | Attribution 4.0 International | 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. © The Author(s) 2016. | Source Title: | Scientific Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/179790 | ISSN: | 2045-2322 | DOI: | 10.1038/srep36382 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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