Discussion
Our study revealed a critical mechanism of adipocytes browning progression and provided a potential target for the treatment of related diseases.
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.