Aging is associated with increased FGF21 levels but unaltered FGF21 responsiveness in adipose tissue
Gallego-Escuredo, José M.
Mateo, Gracia M.
Domingo, Joan C.
MetadataShow full item record
Fibroblast growth factor 21 (FGF21) has been proposed to be an antiaging hormone on the basis of experimental studies in rodent models. However, circulating FGF21 levels are increased with aging in rodents and humans. Moreover, despite the metabolic health‐promoting effects of FGF21, the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to FGF21. Here, we investigated serum FGF21 levels and expression of genes encoding components of the FGF21response molecular machinery in adipose tissue from healthy elderly individuals (≥70 years old) and young controls. Serum FGF21 levels were increased in elderly individuals and were positively correlated with insulinemia and HOMA‐IR, indices of mildly deteriorated glucose homeostasis. Levels of β‐Klotho, the coreceptor required for cellular responsiveness to FGF21, were increased in subcutaneous adipose tissue from elderly individuals relative to those from young controls, whereas FGF receptor‐1 levels were unaltered. Moreover, total ERK1/2 protein levels were decreased in elderly individuals in association with an increase in the ERK1/2 phosphorylation ratio relative to young controls. Adipose explants from aged and young mice respond similarly to FGF21 “ex vivo”. Thus, in contrast to what is observed in obesity and diabetes, high levels of FGF21 in healthy aging are not associated with repressed FGF21‐responsiveness machinery in adipose tissue. The lack of evidence for impaired FGF21 responsiveness in adipose tissue establishes a distinction between alterations in the FGF21 endocrine system in aging and chronic metabolic pathologies.
Is part ofAging Cell, 2018, vol. 17, núm. 5, e12822
European research projects
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as cc-by (c) Joan Villarroya et al., 2018
Showing items related by title, author, creator and subject.
Reciprocal effects of antiretroviral drugs used to treat HIV infection on the fibroblast growth factor 21/β-Klotho System Moure, Ricardo; Domingo, Pere; Villarroya, Joan; Gasa, Laura; Gallego-Escuredo, José M.; Quesada-López, Tania; Morón-Ros, Samantha; Maroto, Alberto F.; Mateo, Gracia M.; Domingo, Joan C.; Villarroya, Francesc; Giralt, Marta (American Society for Microbiology, 2018)Following antiretroviral therapy, HIV-infected patients show increased circulating levels of the antidiabetic hormone fibroblast growth factor 21 (FGF21). In contrast, the expression of the FGF21-obligatory coreceptor ...
Low-Dose Spironolactone-Pioglitazone-Metformin Normalizes Circulating Fetuin-A Concentrations in Adolescent Girls with Polycystic Ovary Syndrome Díaz, Marta; Gallego-Escuredo, José M.; López-Bermejo, Abel; de Zegher, Francis; Villarroya, Francesc; Ibáñez, Lourdes (Hindawi, 2018)Background: Fetuin-A is a glycoprotein produced in the liver and related to metabolic syndrome; fetuin-A secretion is divergently regulated in different pathological conditions. In girls with polycystic ovary syndrome ...
Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance Fourcade, Stéphane; Morató, Laia; Parameswaran, Janani; Ruiz, Montserrat; Ruiz-Cortés, Tatiana; Jové Font, Mariona; Naudí i Farré, Alba; Martínez, Paloma; Dierssen, Mara; Ferrer, Isidre; Villarroya, Francesc; Pamplona Gras, Reinald; Vaquero, Alejandro; Portero Otín, Manuel; Pujol, Aurora (Wiley, 2017)Sirtuin 2 (SIRT2) is a member of a family of NAD+-dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and ...