ArticleNature metabolism2024
Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.
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Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
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Who cites it
23 citing papers in PubMed.
- Peroxisome proliferator-activated receptor gamma (PPARγ) as a mechano-metabolic transducer: coordinating lipid homeostasis through mechanical cues.Molecular biomedicine · 2026Review
- The Mechanobiology of Adipocyte Hypertrophy: Cytoskeletal Remodelling as a Driver of Insulin Resistance in Obesity.Cell biochemistry and function · 2026Review
- The emerging role of the Hippo signaling pathway in interorgan crosstalk.The FEBS journal · 2026Review
- Secretion Patterns of Leptin: A Key Component in the Regulation of Energy Homeostasis and Its Therapeutic Applications.Biomolecules · 2026Review
- Reprogramming in delipidated adipocytes: metabolism, regulation and progress.Cell death discovery · 2026Review
- The Hippo signaling pathway in pediatric brain tumors: molecular mechanisms and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- Concurrent Alterations in DNA Methylation and RNA m6A Methylation During Epigenetic and Transcriptomic Reprogramming Induced by Tail Docking Stress in Fat-Tailed Sheep.Animals : an open access journal from MDPI · 2026Article
- Mechano-matching hydrogel patch promotes myocardial infarction repair via YAP-Bcl-2 pathway activation.Materials today. Bio · 2026Article
- YAP/TAZ-VGLL3 governs adipocyte fate via epigenetic reprogramming of PPARγ and its target enhancers.Science advances · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- ARHGEF3 coordinates adipocyte hypertrophy and differentiation through dual YAP-RhoA and PPARγ activation.Journal of advanced research · 2026Article
- Dual targeting of lipid metabolic reprogramming and immunosuppressive sentinel lymph nodes potentiates anti-metastatic therapy for triple negative breast cancer.Bioactive materials · 2026Article
- Astragaloside IV modulates oxidative stress and osteoimmune-Wnt signaling in ovariectomized rats: an integrated study of RNA sequencing, molecular docking, and experimental validation.Frontiers in nutrition · 2026Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Bioenergetic responses to β-adrenergic stimulation in beige adipocyte depend on actomyosin driven forces.bioRxiv : the preprint server for biology · 2025Article
- Testicular heterochrony in vgll3-mediated maturation age in Atlantic salmon.G3 (Bethesda, Md.) · 2025Article
- Adipocyte-specific Zeb1 downregulation remodels the tumor-associated adipose microenvironment to facilitate female breast cancer progression.Nature communications · 2025Article
- The hippo pathway: a molecular bridge between environmental cues and pace of life.BMC ecology and evolution · 2025Review
- Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype.Nature communications · 2025Article
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Authors and funding
29 authors.
Sungwoo Choi *Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID http://orcid.org/0000-0001-7802-2187
Ju-Gyeong Kang *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.ORCID http://orcid.org/0000-0002-3397-232X
Yen T H TranNational 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.ORCID http://orcid.org/0000-0003-1414-2328
Sun-Hye JeongNational 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.
Kun-Young ParkGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID http://orcid.org/0000-0003-0425-3286
Hyemi ShinGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID http://orcid.org/0000-0002-7445-7834
Young Hoon KimNational 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.
Myungsun ParkGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Hahn NahmgoongNational 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.
Taejun SeolNational 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.ORCID http://orcid.org/0000-0003-1738-9297
Haeyon JeonNational 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.
Yeongmin KimDepartment of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea.ORCID http://orcid.org/0000-0002-8643-7064
Sanghee ParkDepartment of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon, Republic of Korea.ORCID http://orcid.org/0000-0003-1632-3448
Hee-Joo KimDepartment of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea.ORCID http://orcid.org/0000-0002-4469-2075
Min-Seob KimDepartment of Fundamental Environment Research, Environmental Measurement and Analysis Center, National Institute of Environmental Research, Incheon, Republic of Korea.ORCID http://orcid.org/0000-0002-0365-7468
Xiaoxu LiLaboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Maroun Bou SleimanLaboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-1375-7577
Eries LeeGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID http://orcid.org/0000-0002-8977-4998
Jinhyuk ChoiGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
David EisenbarthNational 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.ORCID http://orcid.org/0000-0003-1378-0029
Sang Heon LeeGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Suhyeon ChoNational 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.
David D MooreDepartment of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-5151-9748
Johan AuwerxLaboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-5065-5393
Il-Young KimDepartment of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon, Republic of Korea.ORCID http://orcid.org/0000-0002-6314-2415
Jae Bum KimNational 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.ORCID http://orcid.org/0000-0003-2337-6935
Jong-Eun ParkGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID http://orcid.org/0000-0002-1687-2423
Dae-Sik LimNational 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.ORCID http://orcid.org/0000-0003-2356-7555
Jae Myoung SuhGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. jmsuh@kaist.ac.kr.ORCID http://orcid.org/0000-0001-8097-4662
Funding
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Excellent Science (H2020 Priority Excellent Science) ERC-AdG-787702EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-AdG-787702National Research Foundation of Korea (NRF) 2021R1A2C2007573National Research Foundation of Korea (NRF) 2021R1A2C3005801National Research Foundation of Korea (NRF) NRF-2020-2079551National Research Foundation of Korea (NRF) RS-2023-00218616National Research Foundation of Korea (NRF) RS-2023-00261586
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.
Indexed as
Adaptor Proteins, Signal TransducingAdipocytesAdipose TissueEnergy MetabolismHippo Signaling PathwayLeptinProtein Serine-Threonine KinasesSignal TransductionYAP-Signaling ProteinsAnimalsCell Cycle ProteinsMicePhosphoproteinsTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsAdaptor Proteins, Signal TransducingCell Cycle ProteinsLats1 protein, mouseLATS2 protein, mouseLeptinPhosphoproteinsProtein Serine-Threonine KinasesTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsTumor Suppressor ProteinsWwtr1 protein, mouseYap1 protein, mouseYAP-Signaling Proteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.