Loss of FoxOs in muscle reveals sex-based differences in insulin sensitivity but mitigates diet-induced obesity.

ABSTRACT:

Objective

Gender influences obesity-related complications, including diabetes. Females are more protected from insulin resistance after diet-induced obesity, which may be related to fat accumulation and muscle insulin sensitivity. FoxOs regulate muscle atrophy and are targets of insulin action, but their role in muscle insulin sensitivity and mitochondrial metabolism is unknown.

Methods

We measured muscle insulin signaling, mitochondrial energetics, and metabolic responses to a high-fat diet (HFD) in male and female muscle-specific FoxO1/3/4 triple knock-out (TKO) mice.

Results

In male TKO muscle, insulin-stimulated AKT activation was decreased. AKT2 protein and mRNA levels were reduced and insulin receptor protein and IRS-2 mRNA decreased. These changes contributed t

SUBMITTER: Penniman CM 

PROVIDER: S-EPMC6819874 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature