Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/15704
Angiocrine polyamine production regulates adiposity.
Monelli, Erika | Villacampa, Pilar | Zabala-Letona, Amaia | Martinez-Romero, Anabel | Llena, Judith | Beiroa, Daniel | Gouveia, Leonor | Chivite, Iñigo | Zagmutt, Sebastián | Gama-Perez, Pau | Osorio-Conles, Oscar | Muixi, Laia | Martinez-Gonzalez, Ainara | Castillo, Sandra D | Martín-Martín, Natalia | Castel, Pau | Valcarcel-Jimenez, Lorea | Garcia-Gonzalez, Irene CNIC | Villena, Josep A | Fernandez-Ruiz, Sonia | Serra, Dolors | Herrero, Laura | Benedito, Rui CNIC | Garcia-Roves, Pablo | Vidal, Josep | Cohen, Paul | Nogueiras, Rubén | Claret, Marc | Carracedo, Arkaitz | Graupera, Mariona
Nat Metab. 2022 Mar;4(3):327-343
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.
Adiposity | Endothelial Cells | Animals | Mice | Mice, Inbred C57BL | Obesity | Polyamines
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