Obesity-dependent increase in RalA activity disrupts mitochondrial dynamics in white adipocytes.

ABSTRACT: Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance, and fatty liver disease. Here we report that mitochondria undergo fragmentation and reduced oxidative capacity specifically in inguinal white adipose tissue after feeding mice high fat diet (HFD) by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes from mice fed HFD. Targeted deletion of Rala in white adipocytes prevents the obesity-induced fragmentation of mitochondria and produces mice resistant to HFD-induced weight gain via increased fatty acid oxidation. As a result, these mice also exhibit improved glucose tolerance and liver function. In vitro mechanistic studies revealed that RalA suppresses mitochondrial oxida

SUBMITTER: Xia W 

PROVIDER: S-EPMC10312969 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature