Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease
- PMID: 25450203
- DOI: 10.1016/j.jhep.2014.10.039
Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease
Abstract
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor belonging, together with PPARγ and PPARβ/δ, to the NR1C nuclear receptor subfamily. Many PPARα _target genes are involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPARα activation, in combination with PPARβ/δ agonism, improves steatosis, inflammation and fibrosis in pre-clinical models of non-alcoholic fatty liver disease, identifying a new potential therapeutic area. In this review, we discuss the transcriptional activation and repression mechanisms by PPARα, the spectrum of _target genes and chromatin-binding maps from recent genome-wide studies, paying particular attention to PPARα-regulation of hepatic fatty acid and plasma lipoprotein metabolism during nutritional transition, and of the inflammatory response. The role of PPARα, together with other PPARs, in non-alcoholic steatohepatitis will be discussed in light of available pre-clinical and clinical data.
Keywords: Fatty acid oxidation; Fibrosis; Inflammation; Liver; NAFLD; NASH; PPARα; Steatosis; Transrepression.
Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Similar articles
-
PPARα/γ agonists and antagonists differently affect hepatic lipid metabolism, oxidative stress and inflammatory cytokine production in steatohepatitic rats.Cytokine. 2015 Sep;75(1):127-35. doi: 10.1016/j.cyto.2015.05.031. Epub 2015 Jul 17. Cytokine. 2015. PMID: 26194065
-
PPARα gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis.J Hepatol. 2015 Jul;63(1):164-73. doi: 10.1016/j.jhep.2015.02.019. Epub 2015 Feb 19. J Hepatol. 2015. PMID: 25703085
-
Peroxisome proliferator-activated receptor-α agonist, Wy 14,643, improves metabolic indices, steatosis and ballooning in diabetic mice with non-alcoholic steatohepatitis.J Gastroenterol Hepatol. 2012 Feb;27(2):341-50. doi: 10.1111/j.1440-1746.2011.06939.x. J Gastroenterol Hepatol. 2012. PMID: 21929649
-
The role and regulation of the peroxisome proliferator activated receptor alpha in human liver.Biochimie. 2017 May;136:75-84. doi: 10.1016/j.biochi.2016.12.019. Epub 2017 Jan 8. Biochimie. 2017. PMID: 28077274 Review.
-
Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).Pharmacol Res. 2023 Jun;192:106786. doi: 10.1016/j.phrs.2023.106786. Epub 2023 May 3. Pharmacol Res. 2023. PMID: 37146924 Review.
Cited by
-
Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation.Mol Med. 2024 Oct 26;30(1):186. doi: 10.1186/s10020-024-00945-1. Mol Med. 2024. PMID: 39462343 Free PMC article.
-
Non-alcoholic Fatty Liver Disease as a Canonical Example of Metabolic Inflammatory-Based Liver Disease Showing a Sex-Specific Prevalence: Relevance of Estrogen Signaling.Front Endocrinol (Lausanne). 2020 Sep 18;11:572490. doi: 10.3389/fendo.2020.572490. eCollection 2020. Front Endocrinol (Lausanne). 2020. PMID: 33071979 Free PMC article. Review.
-
Albumin, an interesting and functionally diverse protein, varies from 'native' to 'effective' (Review).Mol Med Rep. 2024 Feb;29(2):24. doi: 10.3892/mmr.2023.13147. Epub 2023 Dec 15. Mol Med Rep. 2024. PMID: 38099350 Free PMC article. Review.
-
Developing the novel diagnostic model and potential drugs by integrating bioinformatics and machine learning for aldosterone-producing adenomas.Front Mol Biosci. 2024 Jan 4;10:1308754. doi: 10.3389/fmolb.2023.1308754. eCollection 2023. Front Mol Biosci. 2024. PMID: 38239411 Free PMC article.
-
Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1β.Cell Mol Life Sci. 2016 Oct;73(20):3809-22. doi: 10.1007/s00018-016-2331-x. Epub 2016 Aug 13. Cell Mol Life Sci. 2016. PMID: 27522544 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
