| First Author | Bellafante E | Year | 2013 |
| Journal | Hepatology | Volume | 57 |
| Issue | 4 | Pages | 1343-56 |
| PubMed ID | 23299802 | Mgi Jnum | J:273497 |
| Mgi Id | MGI:6287992 | Doi | 10.1002/hep.26222 |
| Citation | Bellafante E, et al. (2013) Hepatic-specific activation of peroxisome proliferator-activated receptor gamma coactivator-1beta protects against steatohepatitis. Hepatology 57(4):1343-56 |
| abstractText | Development of hepatic steatosis and its progression to steatohepatitis may be the consequence of dysfunction of several metabolic pathways, such as triglyceride synthesis, very low-density lipoprotein (VLDL) secretion, and fatty acid beta-oxidation. Peroxisome proliferator-activated receptor gamma coactivator-1beta (PGC-1beta) is a master regulator of mitochondrial biogenesis and oxidative metabolism, lipogenesis, and triglyceride (TG) secretion. Here we generated a novel mouse model with constitutive hepatic activation of PGC-1beta and studied the role of this transcriptional coactivator in dietary-induced steatosis and steatohepatitis. Selective activation of PGC-1beta within hepatocytes is able to protect the liver from lipid overload and from progression to fibrosis. The protective function exerted by PGC-1beta is due to its ability to induce mitochondrial oxidative phosphorylation, fatty acid beta-oxidation, and citrate cycle, as well as to decrease oxidative stress and promote TG secretion in the blood stream. These findings bolster the concept that a combined hepatic specific action of PGC-1beta on lipid synthesis and secretion, as well as on mitochondrial biogenesis and function, could protect against steatohepatitis. |
