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DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue

DJ-1 protein is involved in multiple physiological processes, including Parkinson’s disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasis via regulating brown adipose tissue (BAT) activity. DJ-1-deficient mi...

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Autores principales: Wu, Rong, Liu, Xiao-meng, Sun, Jian-guang, Chen, Hong, Ma, Jun, Dong, Meng, Peng, Shengyi, Wang, Ji-qiu, Ding, Jian-qing, Li, Dong-hao, Speakman, John R, Ning, Guang, Jin, Wanzhu, Yuan, Zengqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309696/
https://www.ncbi.nlm.nih.gov/pubmed/28224045
http://dx.doi.org/10.1038/celldisc.2016.54
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author Wu, Rong
Liu, Xiao-meng
Sun, Jian-guang
Chen, Hong
Ma, Jun
Dong, Meng
Peng, Shengyi
Wang, Ji-qiu
Ding, Jian-qing
Li, Dong-hao
Speakman, John R
Ning, Guang
Jin, Wanzhu
Yuan, Zengqiang
author_facet Wu, Rong
Liu, Xiao-meng
Sun, Jian-guang
Chen, Hong
Ma, Jun
Dong, Meng
Peng, Shengyi
Wang, Ji-qiu
Ding, Jian-qing
Li, Dong-hao
Speakman, John R
Ning, Guang
Jin, Wanzhu
Yuan, Zengqiang
author_sort Wu, Rong
collection PubMed
description DJ-1 protein is involved in multiple physiological processes, including Parkinson’s disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasis via regulating brown adipose tissue (BAT) activity. DJ-1-deficient mice reduced body mass, increased energy expenditure and improved insulin sensitivity. DJ-1 deletion also resisted high-fat-diet (HFD) induced obesity and insulin resistance. Accordingly, DJ-1 transgene triggered autonomous obesity and glucose intolerance. Further BAT transplantation experiments clarified DJ-1 regulates energy and glucose homeostasis by modulating BAT function. Mechanistically, we found that DJ-1 promoted PTEN proteasomal degradation via an E3 ligase, mind bomb-2 (Mib2), which led to Akt activation and inhibited FoxO1-dependent Ucp1 (Uncoupling protein-1) expression in BAT. Consistently, ablation of Akt1 mitigated the obesity and BAT dysfunction induced by DJ-1 transgene. These findings define a new biological role of DJ-1 protein in regulating BAT function, with an implication of the therapeutic target in the treatment of metabolic disorders.
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spelling pubmed-53096962017-02-21 DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue Wu, Rong Liu, Xiao-meng Sun, Jian-guang Chen, Hong Ma, Jun Dong, Meng Peng, Shengyi Wang, Ji-qiu Ding, Jian-qing Li, Dong-hao Speakman, John R Ning, Guang Jin, Wanzhu Yuan, Zengqiang Cell Discov Article DJ-1 protein is involved in multiple physiological processes, including Parkinson’s disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasis via regulating brown adipose tissue (BAT) activity. DJ-1-deficient mice reduced body mass, increased energy expenditure and improved insulin sensitivity. DJ-1 deletion also resisted high-fat-diet (HFD) induced obesity and insulin resistance. Accordingly, DJ-1 transgene triggered autonomous obesity and glucose intolerance. Further BAT transplantation experiments clarified DJ-1 regulates energy and glucose homeostasis by modulating BAT function. Mechanistically, we found that DJ-1 promoted PTEN proteasomal degradation via an E3 ligase, mind bomb-2 (Mib2), which led to Akt activation and inhibited FoxO1-dependent Ucp1 (Uncoupling protein-1) expression in BAT. Consistently, ablation of Akt1 mitigated the obesity and BAT dysfunction induced by DJ-1 transgene. These findings define a new biological role of DJ-1 protein in regulating BAT function, with an implication of the therapeutic target in the treatment of metabolic disorders. Nature Publishing Group 2017-02-14 /pmc/articles/PMC5309696/ /pubmed/28224045 http://dx.doi.org/10.1038/celldisc.2016.54 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Wu, Rong
Liu, Xiao-meng
Sun, Jian-guang
Chen, Hong
Ma, Jun
Dong, Meng
Peng, Shengyi
Wang, Ji-qiu
Ding, Jian-qing
Li, Dong-hao
Speakman, John R
Ning, Guang
Jin, Wanzhu
Yuan, Zengqiang
DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
title DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
title_full DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
title_fullStr DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
title_full_unstemmed DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
title_short DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
title_sort dj-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309696/
https://www.ncbi.nlm.nih.gov/pubmed/28224045
http://dx.doi.org/10.1038/celldisc.2016.54
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