Detalle Publicación

FGF15/19 is required for adipose tissue plasticity in response to thermogenic adaptations

Autores: Moron Ros, S.; Uriarte, I.; Berasain Lasarte, María del Carmen; Ávila Zaragoza, Matías Antonio; Sabater Masdeu, M.; Moreno Navarrete, J. M.; Fernandez Real, J. M.; Giralt, M.; Villarroya, F. (Autor de correspondencia); Gavalda Navarro, A. (Autor de correspondencia)
Título de la revista: MOLECULAR METABOLISM
ISSN: 2212-8778
Volumen: 43
Páginas: 101113
Fecha de publicación: 2021
Objective: To determine the role of enterokine FGF15/19 in adipose tissue thermogenic adaptations. Methods: Circulating FGF19 and gene expression (qRT-PCR) levels were assessed in subcutaneous adipose tissue from obese human patients. Effects of experimentally increased FGF15 and FGF19 levels in vivo were determined in mice using adenoviral and adeno-associated vectors. Adipose tissues were characterized in FGF15-null mice under distinct cold-related thermogenic challenges. The analyses spanned metabolic profiling, tissue characterization, histology, gene expression, and immunoblot assays. Results: In humans, FGF19 levels are directly associated with UCP1 gene expression in subcutaneous adipose tissue. Experimental increases in FGF15 or FGF19 induced white fat browning in mice as demonstrated by the appearance of multilocular beige cells and markers indicative of a beige phenotype, including increased UCP1 protein levels. Mice lacking FGF15 showed markedly impaired white adipose tissue browning and a mild reduction in parameters indicative of BAT activity in response to cold-induced environmental thermogenic challenges. This was concomitant with signs of altered systemic metabolism, such as reduced glucose tolerance and impaired cold-induced insulin sensitization. Conclusions: Enterokine FGF15/19 is a key factor required for adipose tissue plasticity in response to thermogenic adaptations. (C) 2020 The Authors. Published by Elsevier GmbH.