@article{18070f69958847ab9fff8fb29f4e13d3,
title = "Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1β",
abstract = "Non-alcoholic fatty liver diseases are the hepatic manifestation of metabolic syndrome. According to the classical pattern of NAFLD progression, de novo fatty acid synthesis has been incriminated in NAFLD progression. However, this hypothesis has been challenged by the re-evaluation of NAFLD development mechanisms together with the description of the role of lipogenic genes in NAFLD and with the recent observation that PGC-1β, a nuclear receptor/transcription factor coactivator involved in the transcriptional regulation of lipogenesis, displays protective effects against NAFLD/NASH progression. In this review, we focus on the implication of lipogenesis and triglycerides synthesis on the development of non-alcoholic fatty liver diseases and discuss the involvement of these pathways in the protective role of PGC-1β toward these hepatic manifestations.",
keywords = "Coactivator, Lipogenesis, Liver, NAFLD, NASH, Nuclear receptor, PGC-1, Steatohepatitis",
author = "Simon Ducheix and Vegliante, {Maria Carmela} and Gaetano Villani and Nicola Napoli and Carlo Sabb{\`a} and Antonio Moschetta",
note = "Funding Information: This work was funded by the Italian Ministry of University and Education (PRIN 2010FHH32M-002), the Italian Ministry of Health (Young Researchers Grant GR-2010-2314703), and Fondazione Umberto Veronesi (FUV). Funding Information: It has been shown that hepatic overexpression of human PGC-1β in mice protects against NASH and steatosis induced by MCD and HFD, respectively []. In this model, at a basal nutritional state, PGC-1β overexpression stimulates mitochondrial functions as well as the expression of genes involved in lipogenesis. When fed an MCD diet, PGC-1β KI livers are protected against triglycerides and cholesterol accumulation, lipid peroxidation, HSCs activation, and apoptosis. The authors proposed that this protection occurs through an increase in mitochondrial biogenesis/function, anti-oxidant defenses, FA oxidation, and triglyceride secretion. This was supported by the observed increase of nuclear respiratory factor-2 (NRF-2) mediated stress response and by the role of PGC-1β as coactivator of the peroxisome proliferator-activated receptor α (PPARα) [] and the forkhead box O2 (FoxO2) [] transcription factors, involved in β-oxidation [] and very low-density lipoprotein (VLDL) secretion [, ], respectively. Publisher Copyright: {\textcopyright} 2016, Springer International Publishing.",
year = "2016",
month = oct,
day = "1",
doi = "10.1007/s00018-016-2331-x",
language = "English (US)",
volume = "73",
pages = "3809--3822",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "20",
}