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

Keywords

  • mechanisms of disease
  • ubiquitylation

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    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, J. R., Ning, G., Jin, W., & Yuan, Z. (2017). DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue. Cell discovery, 3, [16054]. https://doi.org/10.1038/celldisc.2016.54