PMID- 37251330
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230531
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - PTPN2 targets TAK1 for dephosphorylation to improve cellular senescence and 
      promote adipose tissue browning in T2DM.
PG  - 1124633
LID - 10.3389/fphar.2023.1124633 [doi]
LID - 1124633
AB  - 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-kappaB 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.
CI  - Copyright (c) 2023 Liu, Han, Zhu, Song, Zhang, Meng, Zhang, Zhang and Zhong.
FAU - Liu, Yapeng
AU  - Liu Y
AD  - 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.
FAU - Han, Lu
AU  - Han L
AD  - 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.
AD  - Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, Shandong, China.
FAU - Zhu, Ping
AU  - Zhu P
AD  - 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.
FAU - Song, Ming
AU  - Song M
AD  - 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.
FAU - Zhang, Yaoyuan
AU  - Zhang Y
AD  - 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.
FAU - Meng, Linlin
AU  - Meng L
AD  - 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.
FAU - Zhang, Wei
AU  - Zhang W
AD  - 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.
FAU - Zhang, Cheng
AU  - Zhang C
AD  - 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.
FAU - Zhong, Ming
AU  - Zhong M
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20230512
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10213551
OTO - NOTNLM
OT  - PTPN2
OT  - TAK1
OT  - adipocytes
OT  - adipose tissue browning
OT  - senescence
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/30 13:07
MHDA- 2023/05/30 13:08
PMCR- 2023/05/12
CRDT- 2023/05/30 11:35
PHST- 2022/12/15 00:00 [received]
PHST- 2023/04/19 00:00 [accepted]
PHST- 2023/05/30 13:08 [medline]
PHST- 2023/05/30 13:07 [pubmed]
PHST- 2023/05/30 11:35 [entrez]
PHST- 2023/05/12 00:00 [pmc-release]
AID - 1124633 [pii]
AID - 10.3389/fphar.2023.1124633 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 May 12;14:1124633. doi: 10.3389/fphar.2023.1124633. 
      eCollection 2023.