Published in
Springer Nature [academic journals on nature.com], Cell Death & Differentiation, 3(30), p. 766-778, 2022
DOI: 10.1038/s41418-022-01077-x
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Blockage of PPARγ T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions
,
Qiang Tian,
Qiuping Wang,
Yan Lu,
Luchen Sun,
Sijie Wang,
Yuncheng Bei,
Jianguo Ji,
Hu Zhou ,
Wei Yang ,
Pengju Yao,
Wenyuan Zhu,
Lingyun Sun,
Zhifeng Huang
and other authors.
Full text: Unavailable
Abstract
AbstractBeige 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 PPARγ regulates the inducibility of beige adipocytes. This unique posttranslational modification (PTM) pattern influences allosteric communication between PPARγ and DNA or coactivators, which impedes the PPARγ-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 PPARγ agonists for the treatment of obesity and related metabolic disorders.