Cover Story Current Issue

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP) and CO2 using GTP as a phosphate donor. PCK1 is tightly regulated at the transcriptional level and is highly induced during fasting, especially in the liver.

Full text

 

Current Issue

Deubiquitinating Enzyme USP2 Regulates Brown Adipose Tissue Thermogenesis via Controlling EBF2 Stabilization

Yuejie Xu, Ying Chen, Ningning Bai, Yingying Su, ... Jiemin Pan

Objective

The activation of brown adipose tissue (BAT) promotes energy expenditure is recognized as a promising therapeutic strategy for combating obesity. The deubiquitinating enzyme family members are widely involved in the process of energy metabolism. However, the specific deubiquitinating enzyme member that affects the BAT thermogenesis remains largely unexplored.

Methods

Adeno-associated virus, lentivirus and small molecule inhibitor were applied to generate USP2 gain- or loss-of-function both in vivo and in vitro. OxyMax comprehensive laboratory animal monitoring system, seahorse and transmission electron microscopy were used to determine the energy metabolism. Quantitative proteomics, immunofluorescence staining and co-immunoprecipitation were performed to reveal the potential substrates of USP2.

Results

USP2 is upregulated upon thermogenic activation in adipose, and has a close correlation with UCP1 mRNA levels in human adipose tissue. BAT-specific Usp2 knockdown or systemic USP2 inhibition resulted in impaired thermogenic programs both in vivo and in vitro. Conversely, overexpression of Usp2 in BAT conferred protection against high-fat diet-induced obesity and associated metabolic disorders. Proteome-wide analysis identified EBF2 as the substrate of USP2 that mediates the thermogenic function of USP2 in BAT.

Conclusions

Our data demonstrated the vital role of USP2 in regulating BAT activation and systemic energy homeostasis. Activation of USP2-EBF2 interaction could be a potential therapeutic strategy against obesity.

Articles in Press

Deubiquitinating Enzyme USP2 Regulates Brown Adipose Tissue Thermogenesis via Controlling EBF2 Stabilization

Yuejie Xu, Ying Chen, Ningning Bai, Yingying Su, ... Jiemin Pan

Objective

The activation of brown adipose tissue (BAT) promotes energy expenditure is recognized as a promising therapeutic strategy for combating obesity. The deubiquitinating enzyme family members are widely involved in the process of energy metabolism. However, the specific deubiquitinating enzyme member that affects the BAT thermogenesis remains largely unexplored.

Methods

Adeno-associated virus, lentivirus and small molecule inhibitor were applied to generate USP2 gain- or loss-of-function both in vivo and in vitro. OxyMax comprehensive laboratory animal monitoring system, seahorse and transmission electron microscopy were used to determine the energy metabolism. Quantitative proteomics, immunofluorescence staining and co-immunoprecipitation were performed to reveal the potential substrates of USP2.

Results

USP2 is upregulated upon thermogenic activation in adipose, and has a close correlation with UCP1 mRNA levels in human adipose tissue. BAT-specific Usp2 knockdown or systemic USP2 inhibition resulted in impaired thermogenic programs both in vivo and in vitro. Conversely, overexpression of Usp2 in BAT conferred protection against high-fat diet-induced obesity and associated metabolic disorders. Proteome-wide analysis identified EBF2 as the substrate of USP2 that mediates the thermogenic function of USP2 in BAT.

Conclusions

Our data demonstrated the vital role of USP2 in regulating BAT activation and systemic energy homeostasis. Activation of USP2-EBF2 interaction could be a potential therapeutic strategy against obesity.

Save the Date

12th Helmholtz 
Diabetes Conference 
22-24. Sep, Munich

You are what you eat

Here is a video of Vimeo. When the iframes is activated, a connection to Vimeo is established and, if necessary, cookies from Vimeo are also used. For further information on cookies policy click here.

Auf Werbeinhalte, die vor, während oder nach Videos von WEBSITE-URL eingeblendet werden, hat WEBSITE-URL keinen Einfluss. Wir übernehmen keine Gewähr für diese Inhalte. Weitere Informationen finden Sie hier.