FGF21 induces autophagy-mediated cholesterol efflux to inhibit atherogenesis via RACK1 up-regulation.

ABSTRACT: Fibroblast growth factor 21 (FGF21) acts as an anti-atherosclerotic agent. However, the specific mechanisms governing this regulatory activity are unclear. Autophagy is a highly conserved cell stress response which regulates atherosclerosis (AS) by reducing lipid droplet degradation in foam cells. We sought to assess whether FGF21 could inhibit AS by regulating cholesterol metabolism in foam cells via autophagy and to elucidate the underlying molecular mechanisms. In this study, ApoE^-/- mice were fed a high-fat diet (HFD) with or without FGF21 and FGF21 + 3-Methyladenine (3MA) for 12 weeks. Our results showed that FGF21 inhibited AS in HFD-fed ApoE^-/- mice, which was reversed by 3MA treatment. Moreover, FGF21 increased plaque RACK1 and autophagy-related protein (LC3 a

SUBMITTER: Xiaolong L 

PROVIDER: S-EPMC7205825 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature