1. Role and therapeutic potential of dietary ketone bodies in lymph vessel growth
- Author
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Ann Bouché, Massimiliano Mazzone, Joris Souffreau, Stefan Vinckier, Mieke Dewerchin, Rosa Martín-Pérez, Bart Ghesquière, Peter Carmeliet, Anh-Co Khanh Truong, Pauline de Zeeuw, Ivo Cornelissen, Annalisa Zecchin, Wesley Vermaelen, Laure-Anne Teuwen, Melissa García-Caballero, and Guy Eelen
- Subjects
medicine.medical_specialty ,Ketogenic ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,government.form_of_government ,Ketone Bodies ,Mice ,Immune system ,Physiology (medical) ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Humans ,OXCT1 ,Lymphatic Vessels ,Diet, Ketogenic ,Oxidation-Reduction ,Diet ,Chemistry ,Cell Biology ,Lymphangiogenesis ,Lymphatic Endothelium ,Endocrinology ,Lymphatic system ,Ketone bodies ,government ,sense organs ,Lymph ,Ketogenic diet - Abstract
Lymphatic vessels (LVs), lined by lymphatic endothelial cells (LECs), are indispensable for life1. However, the role of metabolism in LECs has been incompletely elucidated. In the present study, it is reported that LEC-specific loss of OXCT1, a key enzyme of ketone body oxidation2, reduces LEC proliferation, migration and vessel sprouting in vitro and impairs lymphangiogenesis in development and disease in Prox1ΔOXCT1 mice. Mechanistically, OXCT1 silencing lowers acetyl-CoA levels, tricarboxylic acid cycle metabolite pools, and nucleotide precursor and deoxynucleotide triphosphate levels required for LEC proliferation. Ketone body supplementation to LECs induces the opposite effects. Notably, elevation of lymph ketone body levels by a high-fat, low-carbohydrate ketogenic diet or by administration of the ketone body β-hydroxybutyrate increases lymphangiogenesis after corneal injury and myocardial infarction. Intriguingly, in a mouse model of microsurgical ablation of LVs in the tail, which repeats features of acquired lymphoedema in humans, the ketogenic diet improves LV function and growth, reduces infiltration of anti-lymphangiogenic immune cells and decreases oedema, suggesting a novel dietary therapeutic opportunity. ispartof: Nature Metabolism vol:1 issue:7 pages:666-675 ispartof: location:Germany status: Published online
- Published
- 2019