Hepatic peroxisome proliferator‐activated receptor γ coactivator 1β drives mitochondrial and anabolic signatures that contribute to hepatocellular carcinoma progression in mice

• DOI: 10.1002/hep.29484
• Publication Date: 2017-08-31T12:11:27Z
• Authors: Elena Piccinin; Claudia Peres; Elena Bellafante; Simon Ducheix; Claudio Pinto; Gaetano Villani; Antonio Moschetta
• Keywords: Lipogenesis; Tumor progression

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1 β) is a master regulator of mitochondrial biogenesis and oxidative metabolism as well antioxidant defense. Specifically, in the liver, PGC-1β also promotes de novo lipogenesis, thus sustaining cellular anabolic processes. Given relevant pathogenic role fatty acid hepatocarcinoma (HCC), here we pointed to putative novel transcriptional player development progression HCC. For this purpose, generated both hepatic-specific PGC-1β-overexpressing (LivPGC-1β) knockout (LivPGC-1βKO) mice, challenged them with chemical genetic models hepatic carcinogenesis. Our results demonstrate pivotal driving liver tumor development. Indeed, whereas mice overexpressing show greater susceptibility, are protected from High levels able boost reactive oxygen species (ROS) scavenger expression, therefore limiting detrimental ROS accumulation and, consequently, apoptosis. Moreover, it supports anabolism, enhancing expression genes involved triglyceride synthesis. Accordingly, specific ablation ROS-driven macromolecule damage, finally growth.The present data elect gatekeeper function redox status HCC, orchestrating different metabolic programs that allow progression. (Hepatology 2018;67:884-898).