Professor Shen Pingping's team from Nanjing University has made new progress in the field of PPAR?post-translational modification to regulate cellular metabolic reprogramming mechanism

The nuclear receptor PPARg (Peroxisome proliferator-activated receptor gamma) is a molecular receptor that senses external matter and energy signals, and is also an effector
that controls the flow of cell metabolism and regulates cell fate.
In recent years, Professor Shen Pingping's team of Nanjing University has achieved a series of research results in the analysis of protein machinery related to PPAR g post-translational modification, and the identification of key metabolic regulatory molecular elements, which have been published in Signal Transduct Target Ther and Nat Commun, Adv Sci and other magazines
.
The metabolic reprogramming system developed based on this has also been applied to the construction of new cell therapies, and the relevant results have started clinical research and translation
.

       Recently, Professor Shen Pingping's team and the team of Academician Li Xiaokun of Wenzhou Medical University have made another important breakthrough in this field: for the first time in the DNA-binding region of PPAR g ( DNA binding domain (DBD) identified a novel post-translational modification mode, T166 phosphorylation, and confirmed that it is a molecule that controls the differentiation and development of beige adipocytes "Switch" (Figure 1).

Further mechanistic studies have found that the T166 site is located in the center of the two zinc finger structures of the DBD of PPARg when the site is PKC by protein kinase aWhen catalyzed and phosphorylation modification occurs, the DBD conformation can be changed, and the binding of ligand binding domain (LBD) and transcriptional cofactors can be affected by allosteric regulation, and then PPAR can be regulated The transcriptional activity and transcriptional preference of g affect the differentiation of beige adipocytes and the homeostasis
of glycolipid metabolism in the body.
In view of the important regulatory role of phosphorylation of PPAR g T166 in the metabolic reprogramming of fat cells, this study further targets PKC a-PPARg The molecular interaction was linked, and the corresponding gene/chemical intervention strategy was designed and successfully applied in animal models, which efficiently induced the biogenesis of beige adipocytes and improved metabolic disorders such as insulin resistance and hyperlipidemia
.
This study not only proposes a new mechanism and theory of PPAR g post-translational modification to regulate adipocyte differentiation and metabolic function, but also broadens the understanding of PPAR g The understanding of biological functions also provides a new way
to promote the differentiation of beige adipocytes and treat metabolic diseases.

PKC a-mediated phosphorylation of PPARgT166 controls beige adipocytes differentiation and remodeling cellular lipid metabolism homeostasis

       Currently, the research results are titled "Blockage of PPARγ T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions", 2022 Published
online on November 3 in Cell death & Differentiation.
The link to the paper is style="line-height:150%;font-family:;color:#333333;" _mstmutation="1" _istranslated="1">
.
Nanfei Yang, a doctoral student at Nanjing University, is the first author of the paper, Professor Shen Pingping, School of Life Sciences, Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, and Academician Li Xiaokun, School of Pharmacy/Oujiang Laboratory of Wenzhou Medical University, are the co-corresponding authors
of the paper.
Professor Jianguo Ji from the School of Life Sciences of Peking University, Sun Lingyun, Director of Nanjing Gulou Hospital, Professor Huang Zhifeng from the School of Pharmacy of Wenzhou Medical University, Professor Zhou Hu from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Professor Yang Wei from the University of California, Los Angeles are co-scientists
of the study.
The research work was supported by the National Key R&D Program of the Ministry of Science and Technology "Protein Machinery and Life Process Regulation" (2017YFA0506000) and the Guangdong Provincial Basic and Applied Basic Research Fund Regional Joint Fund Project (Key Project) (2021B1515120016
。