Hepatic follistatin increases basal metabolic rate and attenuates diet-induced obesity during hepatic insulin resistance.

ABSTRACT:

Objective

Body weight change and obesity follow the variance of excess energy input balanced against tightly controlled EE (energy expenditure). Since insulin resistance can reduce energy storage, we investigated whether genetic disruption of hepatic insulin signaling reduced adipose mass with increased EE.

Methods

Insulin signaling was disrupted by genetic inactivation of Irs1 (Insulin receptor substrate 1) and Irs2 in hepatocytes of LDKO mice (Irs1^L/L·Irs2^L/L·Cre^Alb), creating a state of complete hepatic insulin resistance. We inactivated FoxO1 or the FoxO1-regulated hepatokine Fst (Follistatin) in the liver of LDKO mice by intercrossing LDKO mice with FoxO1^L/L or Fst^L/L mice. We used DEXA (dual-energy X-ray absorptiom

SUBMITTER: Tao R 

PROVIDER: S-EPMC10033741 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature