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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2018 (publ. 2017, arch)     Display Documents



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ID: 744088.0, MPI für molekulare Biomedizin / Jahrbuch 2018 (publ. 2017, arch)
The role of fatty acid beta-oxidation in lymphangiogenesis
Authors:Wong, B. W.; Wang, X.; Zecchin, A.; Thienpont, B.; Cornelissen, I.; Kalucka, J.; Garcia-Caballero, M.; Missiaen, R.; Huang, H.; Bruning, U.; Blacher, S.; Vinckier, S.; Goveia, J.; Knobloch, M.; Zhao, H.; Dierkes, C.; Shi, C.; Hagerling, R.; Moral-Darde, V.; Wyns, S.; Lippens, M.; Jessberger, S.; Fendt, S. M.; Luttun, A.; Noel, A.; Kiefer, F.; Ghesquiere, B.; Moons, L.; Schoonjans, L.; Dewerchin, M.; Eelen, G.; Lambrechts, D.; Carmeliet, P.
Date of Publication (YYYY-MM-DD):2017-02-02
Title of Journal:Nature
Volume:542
Issue / Number:7639
Start Page:49
End Page:54
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid beta-oxidation, impairs lymphatic development. LECs use fatty acid beta-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid beta-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1-target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Notably, blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl coenzyme A by supplementing acetate rescues this process in vivo.
External Publication Status:published
Document Type:Article
Communicated by:MPI für molekulare Biomedizin
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Laboratory of Angiogenesis and Vascular Metabolism, VIB Vesalius Research Center, VIB, Leuven B-3000, Belgium. Laboratory of Translational Genetics, Department of Oncology, KU Leuven, Leuven B-3000, Belgium. Laboratory of Translational Genetics, VIB Vesalius Research Center, VIB, Leuven B-3000, Belgium. Laboratory of Biology of Tumor and Development, Groupe Interdisciplinaire de Genoproteomique Appliquee-Cancer (GIGA-Cancer), University of Liege, Liege B-4000, Belgium. Brain Research Institute, Faculty of Medicine and Science, University of Zurich, Zurich 8057, Switzerland. Mammalian Cell Signaling Laboratory, Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Munster 48161, Germany. Metabolomics Core Facility, VIB Vesalius Research Center, VIB, Leuven B-3000, Belgium. Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Vesalius Research Center, VIB, B-3000 Leuven, Belgium. Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), B-3000 Leuven, Belgium. Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven B-3000, Belgium. Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven B-3000, Belgium.
Identifiers:ISSN:1476-4687 (Electronic) 0028-0836 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28024299 [ID No:2]
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