Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Autor: Choi S; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.; National 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., Kang JG; National 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., Tran YTH; National 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., Jeong SH; National 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., Park KY; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Shin H; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Kim YH; National 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., Park M; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Nahmgoong H; National 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., Seol T; National 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., Jeon H; National 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., Kim Y; Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea., Park S; Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon, Republic of Korea., Kim HJ; Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea., Kim MS; Department of Fundamental Environment Research, Environmental Measurement and Analysis Center, National Institute of Environmental Research, Incheon, Republic of Korea., Li X; Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland., Bou Sleiman M; Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland., Lee E; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Choi J; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Eisenbarth D; National 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., Lee SH; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Cho S; National 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., Moore DD; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA., Auwerx J; Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland., Kim IY; Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon, Republic of Korea., Kim JB; National 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., Park JE; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Lim DS; National 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. daesiklim@kaist.ac.kr., Suh JM; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. jmsuh@kaist.ac.kr.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2024 May; Vol. 6 (5), pp. 847-860. Date of Electronic Publication: 2024 May 29.
DOI: 10.1038/s42255-024-01045-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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