Differential gene expression analysis in liver, inguinal white adipose tissue (iWAT), skeletal muscle, and hypothalamus of mice with liver-specific Crif1 deficiency

CR6-interacting factor-1 (CRIF1) interacting with large mitoribosome subunits is essential for the maturation and insertion of oxidative phosphorylation (OxPhos) polypeptides into the mitochondrial inner membrane. Recently, it has reported that the genetic ablation of Crif1 in a tissue-specific manner results in mitochondrial stress response (MSR) including mitochondrial unfolded protein response (UPRmt). In this study, we aim to obtain a comprehensive understanding of systemic energy metabolism in response to hepatic mitochondrial dysfunction. Through the liver-specific Crif1 deficient mice (LKO), we explore the adaptive response not only in the liver but also in inguinal white adipose tissue (iWAT). Moreover, RNA sequencing in liver, iWAT, skeletal muscle, and hypothalamus suggest that hepatic mitochondrial dysfunction enhance metabolic pathways, including glycolysis, fatty acid elongation and degradation, and 1C metabolism in liver and insulin signaling in iWAT. RNA sequencing also suggests that hepato-mitokines, GDF15 and FGF21 are highly increased in liver of LKO mice. To identify the role of hepato-mitokines, we generate double knockout mice (LKO/Gdf15-/- and LKO/Fgf21-/-), suggesting that GDF15 is responsible for the regulation of the body and fat mass and FGF21 has a critical role for the insulin sensitivity and energy expenditure in this mice. RNA was isolated from liver, inguinal adipose tissue (iWAT), skeletal muscle, and hypothalamus of control (Ctrl) and liver-specific Crif1 deficient mice (LKO) fed a chow diet at 8 weeks old of age (n = 3 each per group).