Angiocrine polyamine production regulates adiposity
Creators
- Monelli, E.1
- Villacampa, P.1
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Zabala-Letona, A.2
- Martinez-Romero, A.1
- Llena, J.1
- Beiroa, D.3
- Gouveia, L.1
- Chivite, I.4
- Zagmutt, S.5
- Gama-Perez, P.6
- Osorio-Conles, O.7
- Muixi, L.1
- Martinez-Gonzalez, A.2
- Castillo, S.D.2
- Martin-Martin, N.2
- Castel, P.8
- Valcarcel-Jimenez, L.2
- Garcia-Gonzalez, I.9
- Villena, J.A.10
- Fernandez-Ruiz, S.2
- Serra, D.11
- Herrero, L.11
- Benedito, R.9
- Garcia-Roves, P.11
- Vidal, J.7
- Cohen, P.12
- Nogueiras, R.3
- Claret, M.4
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Carracedo, A.2
-
Graupera, M.1
- 1. Endothelial Pathobiology and Microenviroment Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain
- 2. Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain
- 3. CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
- 4. Neuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- 5. Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain
- 6. Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona and Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
- 7. Department of Endocrinology, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain
- 8. Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA
- 9. Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- 10. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
- 11. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- 12. Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USA
Description
Reciprocal interactions between endothelial cells (ECs) and adipocytes are fundamental to maintain white adipose tissue (WAT) homeostasis, as illustrated by the activation of angiogenesis upon WAT expansion, a process that is impaired in obesity. However, the molecular mechanisms underlying the crosstalk between ECs and adipocytes remain poorly understood. Here, we show that local production of polyamines in ECs stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. We promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss leads to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid β-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by ECs. Our results indicate that angiocrine metabolic signals are important for WAT homeostasis and organismal metabolism.
Files
2022 Monelli Nat Metab.pdf
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(12.4 MB)
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