Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1β protects against steatohepatitis

Elena Bellafante, Stefania Murzilli, Lorena Salvatore, Dominga Latorre, Gaetano Villani, Antonio Moschetta

Research output: Contribution to journalArticle

Abstract

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 β-oxidation. Peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β) 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-1β and studied the role of this transcriptional coactivator in dietary-induced steatosis and steatohepatitis. Selective activation of PGC-1β within hepatocytes is able to protect the liver from lipid overload and from progression to fibrosis. The protective function exerted by PGC-1β is due to its ability to induce mitochondrial oxidative phosphorylation, fatty acid β-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-1β on lipid synthesis and secretion, as well as on mitochondrial biogenesis and function, could protect against steatohepatitis.

Original languageEnglish
Pages (from-to)1343-1356
Number of pages14
JournalHepatology
Volume57
Issue number4
DOIs
Publication statusPublished - Apr 2013

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1β protects against steatohepatitis'. Together they form a unique fingerprint.

  • Cite this

    Bellafante, E., Murzilli, S., Salvatore, L., Latorre, D., Villani, G., & Moschetta, A. (2013). Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1β protects against steatohepatitis. Hepatology, 57(4), 1343-1356. https://doi.org/10.1002/hep.26222