| Title | The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis |
| Authors | Shen, Hongyu Huang, Xun Zhao, Yiheng Wu, Dongmei Xue, Kaili Yao, Jingfei Wang, Yushuang Tang, Nan Qiu, Yifu |
| Affiliation | Peking Univ, Coll Future Technol, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China Natl Inst Biol Sci, Beijing 102206, Peoples R China Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res, Beijing 100084, Peoples R China |
| Keywords | TGF-BETA PPAR-GAMMA EXPRESSION OBESITY COMPLEX YAP PROLIFERATION INFLAMMATION PROGENITORS DYSFUNCTION |
| Issue Date | 13-Oct-2022 |
| Publisher | NATURE COMMUNICATIONS |
| Abstract | Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGF beta stimulation. Fibrosis disrupts adipose tissue (AT) homeostasis and exacerbates metabolic dysfunction upon chronic caloric excess. The molecular mechanisms linking adipocyte plasticity to AT fibrosis are largely unknown. Here we show that the Hippo pathway is coupled with TGF beta signaling to orchestrate a cellular and/or functional shift of adipocytes from energy storage to extracellular matrix (ECM) remodeling in AT fibrosis. We found that Lats1/2-knockout adipocytes could dedifferentiate into DPP4(+) progenitor cells and convert to DPP4(-) myofibroblasts upon TGF beta stimulation. On the other hand, Hippo pathway inhibition during obesity impaired adipocyte identity while promoted ECM remodeling activity of adipocytes. Macrophages recruited by CCL2 produced TGF beta to accelerate AT fibrosis. YAP and TAZ, the Hippo downstream effectors, enhanced SMAD2 stability to promote fibrotic responses. Importantly, inhibition of YAP/TAZ activity in obese mice markedly relieved AT fibrosis and improved metabolic homeostasis. Together, our findings identify the Hippo pathway as a molecular switch in the initiation and development of AT fibrosis, implying it as a therapeutic target. |
| URI | http://hdl.handle.net/20.500.11897/655916 |
| DOI | 10.1038/s41467-022-33800-0 |
| Indexed | SCI(E) |
| Appears in Collections: | 分子医学研究所 生命科学学院 前沿交叉学科研究院 |
