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The role of fatty acid β-oxidation in lymphangiogenesis

Resource type
Authors/contributors
Title
The role of fatty acid β-oxidation in lymphangiogenesis
Abstract
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 β-oxidation, impairs lymphatic development. LECs use fatty acid β-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 β-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.
Publication
Nature
Volume
542
Issue
7639
Pages
49-54
Date
2017/02/02
Journal Abbr
Nature
Language
eng
ISSN
1476-4687
Library Catalog
PubMed
Lipedema Foundation Award
LF04
Citation
Wong, B. W., Wang, X., Zecchin, A., Thienpont, B., Cornelissen, I., Kalucka, J., García-Caballero, M., Missiaen, R., Huang, H., Brüning, U., Blacher, S., Vinckier, S., Goveia, J., Knobloch, M., Zhao, H., Dierkes, C., Shi, C., Hägerling, R., Moral-Dardé, V., … Carmeliet, P. (2017). The role of fatty acid β-oxidation in lymphangiogenesis. Nature, 542(7639), 49–54. https://doi.org/10.1038/nature21028
Topic