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Open AccessJournal ArticleDOI

Peroxisome Proliferator-Activated Receptor Alpha Target Genes

TLDR
An overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPAR α target genes is presented.
Abstract
The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well.

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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

Patricio Godoy, +94 more
TL;DR: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro and how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes.
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A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation

TL;DR: In Inherited defects for most of the FAO enzymes have been identified and characterised and are currently included in neonatal screening programmes and will ultimately lead to better treatment.
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Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease

TL;DR: The molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions are discussed, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.
Journal ArticleDOI

Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease

TL;DR: Nrf2 activity is tightly controlled via CRLKeap1 and SCFβ-TrCP by oxidative stress and energy-based signals, allowing it to mediate adaptive responses that restore redox homeostasis and modulate intermediary metabolism.
Journal ArticleDOI

Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review.

TL;DR: A significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources.
References
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Journal ArticleDOI

Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease

TL;DR: Results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.
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Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators

TL;DR: A member of the steroid hormone receptor superfamily of ligand-activated transcription factors is cloned that is activated by a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.
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Gemfibrozil for the Secondary Prevention of Coronary Heart Disease in Men with Low Levels of High-Density Lipoprotein Cholesterol

TL;DR: Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level, suggesting that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.
Journal ArticleDOI

Peroxisome proliferator-activated receptors: nuclear control of metabolism.

TL;DR: This work has shown that direct expression of PPAR mRNAs in the absence of a specific carrier gene results in down-regulation in the activity of other PPARs, and these properties are consistent with those of a “spatially aggregating substance”.
Journal ArticleDOI

The Mechanisms of Action of PPARs

TL;DR: The current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases is presented.
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