E-MTAB-1825 - Transcription profiling by array of livers from Foxa2 -/- knockout mice and wild-type mice to study bile acid-induced cytokine inflammatory signaling in response to the lack of Foxa2
Released on 19 August 2013, last updated on 3 June 2014
Cytokine signaling has been connected to regulation of metabolism and energy balance. Numerous cytokine gene expression changes are stimulated by accumulation of bile acids in livers of young Foxa2 liver-conditional null mice. We hypothesized that bile acid-induced inflammation in young Foxa2 mutants, once chronic, affects metabolic homeostasis. We found that loss of Foxa2 in the liver results in a premature aging phenotype, including significant weight gain, reduced food intake, and decreased energy expenditure. We show that Foxa2 antagonizes the mammalian target of rapamycin (mTOR) pathway, resulting in increased hepatic lipogenesis and adiposity. While much prior work has focused on adipose tissue in obesity, we discovered a novel age-onset obesity phenotype in a model where genetic deletion occurs only in the liver, underscoring the importance of the role hepatic lipogenesis plays in the development of obesity.
transcription profiling by array, co-expression, dye swap, genetic modification, in vivo, replicate
Bile acid-induced inflammatory signaling in mice lacking Foxa2 in the liver leads to activation of mTOR and age-onset obesity. Irina M. Bochkis, Soona Shin, Klaus H. Kaestner.