| Title | Blockage of PPAR gamma T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions |
| Authors | Yang, Nanfei Wang, Yuxin Tian, Qiang Wang, Qiuping Lu, Yan Sun, Luchen Wang, Sijie Bei, Yuncheng Ji, Jianguo Zhou, Hu Yang, Wei Yao, Pengju Zhu, Wenyuan Sun, Lingyun Huang, Zhifeng Li, Xiaokun Shen, Pingping |
| Affiliation | Nanjing Univ, Med Sch,Dept Rheumatol & Immunol, Affiliated Hosp,State Key Lab Pharmaceut Biotechn, Sch Life Sci,Affiliated Nanjing Drum Tower Hosp, Nanjing 210023, Peoples R China Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA Nanjing Univ, Med Sch, Dept Rheumatol & Immunol, Affiliated Drum Tower Hosp, 321 Zhongshan Rd, Nanjing 210008, Peoples R China Wenzhou Med Univ, Oujiang Lab, Zhejiang Lab Regenerat Med Vis & Brain Hlth, Wenzhou 325035, Zhejiang, Peoples R China Nanjing Univ, Shenzhen Res Inst, Shenzhen 518000, Peoples R China |
| Keywords | ACTIVATED RECEPTOR-GAMMA WHITE ADIPOSE-TISSUE BROWN FAT THERMOGENESIS INFLAMMATION HOMEOSTASIS EXPRESSION LIGAND ROLES |
| Issue Date | Nov-2022 |
| Publisher | CELL DEATH AND DIFFERENTIATION |
| Abstract | Beige adipocytes in mammalian white adipose tissue (WAT) can reinforce fat catabolism and energy expenditure. Promoting beige adipocyte biogenesis is a tantalizing tactic for combating obesity and its associated metabolic disorders. Here, we report that a previously unidentified phosphorylation pattern (Thr166) in the DNA-binding domain of PPAR gamma regulates the inducibility of beige adipocytes. This unique posttranslational modification (PTM) pattern influences allosteric communication between PPAR gamma and DNA or coactivators, which impedes the PPAR gamma-mediated transactivation of beige cell-related gene expression in WAT. The genetic mutation mimicking T166 phosphorylation (p-T166) hinders the inducibility of beige adipocytes. In contrast, genetic or chemical intervention in this PTM pattern favors beige cell formation. Moreover, inhibition of p-T166 attenuates metabolic dysfunction in obese mice. Our results uncover a mechanism involved in beige cell fate determination. Moreover, our discoveries provide a promising strategy for guiding the development of novel PPAR gamma agonists for the treatment of obesity and related metabolic disorders. |
| URI | http://hdl.handle.net/20.500.11897/658092 |
| ISSN | 1350-9047 |
| DOI | 10.1038/s41418-022-01077-x |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
