PTPN2 targets TAK1 for dephosphorylation to improve cellular senescence and promote adipose tissue browning in T2DM

Frontiers in Pharmacology

Pharmacology

Cheng Zhang¹  Yapeng Liu¹  Linlin Meng¹  Ming Song¹  Wei Zhang¹  Ping Zhu¹  Yaoyuan Zhang¹  Ming Zhong¹  Lu Han² 

[1] The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;

关键词: PTPN2;    TAK1;    adipocytes;    senescence;    adipose tissue browning;   

DOI  :  10.3389/fphar.2023.1124633

 received in 2022-12-15, accepted in 2023-04-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: The energy imbalance when energy intake exceeds expenditure acts as an essential factor in the development of insulin resistance (IR). The activity of brown adipose tissue, which is involved in the dissipation of energy via heat expenditure decreases under type 2 diabetic mellitus (T2DM) state when the number of pathological aging adipocytes increases. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates several biological processes by dephosphorylating several cellular substrates; however, whether PTPN2 regulates cellular senescence in adipocytes and the underlying mechanism has not been reported.Methods: We constructed a model of type 2 diabetic mice with PTPN2 overexpression to explore the role of PTPN2 in T2DM.Results: We revealed that PTPN2 facilitated adipose tissue browning by alleviating pathological senescence, thus improving glucose tolerance and IR in T2DM. Mechanistically, we are the first to report that PTPN2 could bind with transforming growth factor-activated kinase 1 (TAK1) directly for dephosphorylation to inhibit the downstream MAPK/NF-κB pathway in adipocytes and regulate cellular senescence and the browning process subsequently.Discussion: Our study revealed a critical mechanism of adipocytes browning progression and provided a potential target for the treatment of related diseases.

【 授权许可】

Unknown   
Copyright © 2023 Liu, Han, Zhu, Song, Zhang, Meng, Zhang, Zhang and Zhong.