한빛사논문
- 조회454
Sungwoo Choi 1,2,9, Ju-Gyeong Kang 2,9, Yen T. H. Tran 2, Sun-Hye Jeong 2, Kun-Young Park 1, Hyemi Shin 1, Young Hoon Kim 2, Myungsun Park 1, Hahn Nahmgoong 3, Taejun Seol 2, Haeyon Jeon 2, Yeongmin Kim 4, Sanghee Park 5, Hee-joo Kim 4, Min-Seob Kim 6, Xiaoxu Li 7, Maroun Bou Sleiman 7, Eries Lee 1, Jinhyuk Choi 1, David Eisenbarth 2, Sang Heon Lee 1, Suhyeon Cho 2, David D. Moore 8, Johan Auwerx 7, Il-Young Kim 5, Jae Bum Kim 3, Jong-Eun Park 1, Dae-Sik Lim 2 & Jae Myoung Suh 1
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
2National Creative Research Center for Cell Plasticity, KAIST Stem Cell Center, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
3National Creative Research Initiatives Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
4Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea.
5Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon, Republic of Korea.
6Department of Fundamental Environment Research, Environmental Measurement and Analysis Center, National Institute of Environmental Research, Incheon, Republic of Korea.
7Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
8Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA.
9These authors contributed equally: Sungwoo Choi, Ju-Gyeong Kang.
Corresponding authors
Correspondence to Dae-Sik Lim or Jae Myoung Suh.
Abstract
Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ–TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo–YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-05-31)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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