Sex differences in high fat diet-induced metabolic alterations correlate with changes in the modulation of GRK2 levels

A differential sex-related sensitivity has been reported in obesity and insulin resistance-related cardio-metabolic diseases, with a lower incidence of these pathologies being observed in young females when compared to age-matched males. However, such relative protection is lost with age. The mechan...

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Detalhes bibliográficos
Autores: Concepción Arcones, Alba, Cruces Sande, Marta, Ramos, Paula, Mayor Menéndez, Federico, Murga Montesinos, Cristina
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/714302
Acesso em linha:http://hdl.handle.net/10486/714302
https://dx.doi.org/10.3390/cells8111464
Access Level:acceso abierto
Palavra-chave:Sex-related differences
estrogens
GRK2
insulin resistance
obesity
metabolic diseases
diabetes
Biología y Biomedicina / Biología
Descrição
Resumo:A differential sex-related sensitivity has been reported in obesity and insulin resistance-related cardio-metabolic diseases, with a lower incidence of these pathologies being observed in young females when compared to age-matched males. However, such relative protection is lost with age. The mechanisms underlying such sex and age-related changes in the susceptibility to diabetes and obesity are not fully understood. Herein, we report that the relative protection that is displayed by young female mice, as compared to male littermates, against some of the metabolic alterations that are induced by feeding a high fat diet (HFD), correlates with a lower upregulation of the protein levels of G protein-coupled receptor kinase (GRK2), which is a key regulator of both insulin and G protein-coupled receptor signaling, in the liver and adipose tissue. Interestingly, when the HFD is initiated in middle-aged (32 weeks) female mice, these animals are no longer protected and display a more overt obese and insulin-resistant phenotype, along with a more evident increase in the GRK2 protein levels in metabolically relevant tissues in such conditions. Our data suggest that GRK2 dosage might be involved in the sex and age-biased sensitivity to insulin resistance-related pathologies