4.8 Article

Angiocrine polyamine production regulates adiposity

期刊

NATURE METABOLISM
卷 4, 期 3, 页码 327-+

出版社

NATURE PORTFOLIO
DOI: 10.1038/s42255-022-00544-6

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资金

  1. la Fundacion BBVA (Ayuda Fundacion BBVA a Equipos de Investigacion Cientifica 2019) [PR19BIOMET0061]
  2. Ministerio de Ciencia, Innovacion y Universidades (MCIU) (Spain) [SAF2017-82072-ERC]
  3. FEDER/EU [SAF2017-89116R-P]
  4. European Regional Developmental Fund (ERDF), a Way to Build Europe
  5. MCEI [PID2020-116184RB-I00]
  6. Catalan Government through the project 2017-SGR
  7. PTEN Research Foundation [BRR-17-001]
  8. La Caixa Foundation [HR19-00120, HR21-00046, 100010434, LCF/PR/HR17, LCF/PR/HR17/52150009]
  9. la Asociacion Espanola contra el Cancer-Grupos Traslacionales [GCTRA18006CARR]
  10. European Foundation for the Study of Diabetes/Lilly research grant
  11. People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013 [317250]
  12. European Union [675392]
  13. Basque Department of Industry, Tourism and Trade (Elkartek)
  14. department of education [IKERTALDE IT1106-16]
  15. MCIU [PID2019-108787RB-I00, SEV-2016-0644, SAF2016-81975-REDT]
  16. Vencer el Cancer foundation
  17. European Research Council (ERC) [819242]
  18. FEDER funds
  19. Instituto de Salud Carlos III (ISCIII)
  20. ERC under the European Union [725004, 810331]
  21. CERCA Programme/Generalitat de Catalunya
  22. MINECO [SAF201783813-C3-1-R]
  23. CIBEROBN [CB06/03/0001]
  24. Government of Catalonia [2017SGR278]
  25. Fundacio La Marato de TV3 [20162730]
  26. FEDER/Ministerio de Ciencia, Innovacion y Universidades-Agencia Estatal de Investigacion [RTI2018-099413-B-I00, RED2018-102379-T]
  27. Xunta de Galicia [2016-PG057, 2020-PG015]
  28. Fundacion BBVA
  29. Fundacion Atresmedia
  30. CIBEROBN
  31. MICINN [RTI2018-099250-B100]
  32. ISCIII [PI15/00701]
  33. ERDF, A Way to Build Europe
  34. Juan de la Cierva [IJCI-2015-23455]
  35. CONICYT fellowship from Chile
  36. Vetenskapsradet (Swedish Research Council) [2018-06591]
  37. NCI K99/R00 Pathway to Independence Award [K99CA245122]
  38. Marie Curie Actions (MSCA) [675392] Funding Source: Marie Curie Actions (MSCA)
  39. Swedish Research Council [2018-06591] Funding Source: Swedish Research Council
  40. European Research Council (ERC) [810331, 725004] Funding Source: European Research Council (ERC)

向作者/读者索取更多资源

Reciprocal interactions between endothelial cells and adipocytes play a crucial role in maintaining the homeostasis of adipose tissue. The production of polyamines in endothelial cells stimulates adipocyte lipolysis and regulates adipose tissue homeostasis.
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 beta-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. Endothelial cells in white adipose tissue are shown to produce polyamines, which regulate adipocyte lipolysis, thus demonstrating how local angiocrine signals contribute to healthy adipose tissue homeostasis.

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