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

Rong Wu; Xiao-Meng Liu; Jian-Guang Sun; Hong Chen; Jun Ma; Meng Dong; Shengyi Peng; Ji-Qiu Wang; Jian-Qing Ding; Dong-Hao Li; John R Speakman; Guang Ning; Wanzhu Jin; Zengqiang Yuan

doi:10.1038/celldisc.2016.54

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

Rong Wu, Xiao-Meng Liu, Jian-Guang Sun, Hong Chen, Jun Ma, Meng Dong, Shengyi Peng, Ji-Qiu Wang, Jian-Qing Ding, Dong-Hao Li, John R Speakman, Guang Ning, Wanzhu Jin, Zengqiang Yuan

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

9 Downloads (Pure)

Abstract

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 homeostasisvia 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.

Original language	English
Article number	16054
Journal	Cell discovery
Volume	3
DOIs	https://doi.org/10.1038/celldisc.2016.54
Publication status	Published - 14 Feb 2017

Bibliographical note

We thank the members of the Yuan laboratory for critical reading of the manuscript and helpful discussion. We thank the Pathology Core Facility in the Institute of Biophysics, CAS. We also thank Dr Joyce Flemmings for the English editing. This work was supported by the grants from the strategic priority research program (XDB13030000 to WJ), the National Science Foundation of China (Grant No. 81125010 and 81030025 to ZY), the National Basic Research Program of China (973–2012CB910701 and 2013DFA31990 to ZY) and Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation (2014–2016) from Chinese Academy of Sciences; and Key research program (KJZD-EW-L01-3 to WJ), One Hundred Talents Program (WJ) of the Chinese Academy of Sciences and from the Ministry of Science and Technology of China (2012CBA01301 and 2012CB944701 to WJ), as well as by a grant from the National Natural Science Foundation of China (31171131 and 81370951 to WJ).

Keywords

mechanisms of disease
ubiquitylation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/celldisc.2016.54Licence: CC BY

DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
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/
Final published version, 4.67 MBLicence: CC BY

Cite this

@article{443864bdf3444927a46d4ecb50e49d2d,

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

abstract = "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 homeostasisvia 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.",

keywords = "mechanisms of disease, ubiquitylation",

author = "Rong Wu and Xiao-Meng Liu and Jian-Guang Sun and Hong Chen and Jun Ma and Meng Dong and Shengyi Peng and Ji-Qiu Wang and Jian-Qing Ding and Dong-Hao Li and Speakman, {John R} and Guang Ning and Wanzhu Jin and Zengqiang Yuan",

note = "We thank the members of the Yuan laboratory for critical reading of the manuscript and helpful discussion. We thank the Pathology Core Facility in the Institute of Biophysics, CAS. We also thank Dr Joyce Flemmings for the English editing. This work was supported by the grants from the strategic priority research program (XDB13030000 to WJ), the National Science Foundation of China (Grant No. 81125010 and 81030025 to ZY), the National Basic Research Program of China (973–2012CB910701 and 2013DFA31990 to ZY) and Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation (2014–2016) from Chinese Academy of Sciences; and Key research program (KJZD-EW-L01-3 to WJ), One Hundred Talents Program (WJ) of the Chinese Academy of Sciences and from the Ministry of Science and Technology of China (2012CBA01301 and 2012CB944701 to WJ), as well as by a grant from the National Natural Science Foundation of China (31171131 and 81370951 to WJ).",

year = "2017",

month = feb,

day = "14",

doi = "10.1038/celldisc.2016.54",

language = "English",

volume = "3",

journal = "Cell discovery",

issn = "2056-5968",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue

AU - Wu, Rong

AU - Liu, Xiao-Meng

AU - Sun, Jian-Guang

AU - Chen, Hong

AU - Ma, Jun

AU - Dong, Meng

AU - Peng, Shengyi

AU - Wang, Ji-Qiu

AU - Ding, Jian-Qing

AU - Li, Dong-Hao

AU - Speakman, John R

AU - Ning, Guang

AU - Jin, Wanzhu

AU - Yuan, Zengqiang

N1 - We thank the members of the Yuan laboratory for critical reading of the manuscript and helpful discussion. We thank the Pathology Core Facility in the Institute of Biophysics, CAS. We also thank Dr Joyce Flemmings for the English editing. This work was supported by the grants from the strategic priority research program (XDB13030000 to WJ), the National Science Foundation of China (Grant No. 81125010 and 81030025 to ZY), the National Basic Research Program of China (973–2012CB910701 and 2013DFA31990 to ZY) and Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation (2014–2016) from Chinese Academy of Sciences; and Key research program (KJZD-EW-L01-3 to WJ), One Hundred Talents Program (WJ) of the Chinese Academy of Sciences and from the Ministry of Science and Technology of China (2012CBA01301 and 2012CB944701 to WJ), as well as by a grant from the National Natural Science Foundation of China (31171131 and 81370951 to WJ).

PY - 2017/2/14

Y1 - 2017/2/14

N2 - 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 homeostasisvia 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.

AB - 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 homeostasisvia 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.

KW - mechanisms of disease

KW - ubiquitylation

U2 - 10.1038/celldisc.2016.54

DO - 10.1038/celldisc.2016.54

M3 - Article

C2 - 28224045

SN - 2056-5968

VL - 3

JO - Cell discovery

JF - Cell discovery

M1 - 16054

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this