Enhanced β-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110α inactivation in adipose tissue.

ABSTRACT: The insulin/IGF-1 signalling pathway is a key regulator of metabolism and the rate of ageing. We previously documented that systemic inactivation of phosphoinositide 3-kinase (PI3K) p110α, the principal PI3K isoform that positively regulates insulin signalling, results in a beneficial metabolic effect in aged mice. Here we demonstrate that deletion of p110α specifically in the adipose tissue leads to less fat accumulation over a significant part of adult life and allows the maintenance of normal glucose tolerance despite insulin resistance. This effect of p110α inactivation is due to a potentiating effect on β-adrenergic signalling, which leads to increased catecholamine-induced energy expenditure in the adipose tissue. Our findings provide a paradigm of how partial inactivation of an esse

SUBMITTER: Araiz C 

PROVIDER: S-EPMC6449391 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature