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

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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 languageEnglish
Article number16054
JournalCell discovery
Volume3
DOIs
Publication statusPublished - 14 Feb 2017

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Brown Adipose Tissue
Homeostasis
Tissue
Glucose
Obesity
Transgenes
Insulin Resistance
Insulin
Transplantation (surgical)
Proteins
Ubiquitin-Protein Ligases
Physiological Phenomena
Bombs
Tissue Transplantation
Nutrition
Ablation
Energy balance
Glucose Intolerance
Metabolism
High Fat Diet

Keywords

  • mechanisms of disease
  • ubiquitylation

Cite this

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.

In: Cell discovery, Vol. 3, 16054, 14.02.2017.

Research output: Contribution to journalArticle

Wu, R, Liu, X-M, Sun, J-G, Chen, H, Ma, J, Dong, M, Peng, S, Wang, J-Q, Ding, J-Q, Li, D-H, Speakman, JR, Ning, G, Jin, W & Yuan, Z 2017, 'DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue', Cell discovery, vol. 3, 16054. https://doi.org/10.1038/celldisc.2016.54
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. In: Cell discovery. 2017 ; Vol. 3.
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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.",
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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).",
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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

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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.

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