| First Author | Piccinin E | Year | 2018 |
| Journal | Hepatology | Volume | 67 |
| Issue | 3 | Pages | 884-898 |
| PubMed ID | 28857232 | Mgi Jnum | J:272240 |
| Mgi Id | MGI:6282977 | Doi | 10.1002/hep.29484 |
| Citation | Piccinin E, et al. (2018) Hepatic peroxisome proliferator-activated receptor gamma coactivator 1beta drives mitochondrial and anabolic signatures that contribute to hepatocellular carcinoma progression in mice. Hepatology 67(3):884-898 |
| abstractText | The peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1beta (PGC-1 beta) is a master regulator of mitochondrial biogenesis and oxidative metabolism as well as of antioxidant defense. Specifically, in the liver, PGC-1beta also promotes de novo lipogenesis, thus sustaining cellular anabolic processes. Given the relevant pathogenic role of mitochondrial and fatty acid metabolism in hepatocarcinoma (HCC), here we pointed to PGC-1beta as a putative novel transcriptional player in the development and progression of HCC. For this purpose, we generated both hepatic-specific PGC-1beta-overexpressing (LivPGC-1beta) and PGC-1beta knockout (LivPGC-1betaKO) mice, and we challenged them with both chemical and genetic models of hepatic carcinogenesis. Our results demonstrate a pivotal role of PGC-1beta in driving liver tumor development. Indeed, whereas mice overexpressing PGC-1beta show greater tumor susceptibility, PGC-1beta knockout mice are protected from carcinogenesis. High levels of PGC-1beta are able to boost reactive oxygen species (ROS) scavenger expression, therefore limiting the detrimental ROS accumulation and, consequently, apoptosis. Moreover, it supports tumor anabolism, enhancing the expression of genes involved in fatty acid and triglyceride synthesis. Accordingly, the specific hepatic ablation of PGC-1beta promotes the accumulation of ROS-driven macromolecule damage, finally limiting tumor growth. CONCLUSION: The present data elect hepatic PGC-1beta as a transcriptional gatekeeper of mitochondrial function and redox status in HCC, orchestrating different metabolic programs that allow tumor progression. (Hepatology 2018;67:884-898). |
