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Cited by 1,020Peroxisome Proliferator-Activated ReceptorsCholesterol and Lipid MetabolismParaoxonase enzyme and polymorphisms

Peroxisome Proliferator-Activated Receptor Alpha Target Genes

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Rakhshandehroo, Maryam, Knoch, Bianca, Müller, Michael, Kersten, Sander·2010·PPAR Research
DOI 10.1155/2010/612089PMC PMC2948931
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Abstract

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

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  • The PPAR-RXR dimer binds peroxisome proliferator response elements (PPRE) to activate transcription of ATP-binding cassette (ABC) family genes and genes involved in fatty acid scavenging and lipid metabolism.

    “The PPAR-RXR dimer binds peroxisome proliferator response elements (PPRE) to activate the transcription of genes within the ATP-binding cassette (ABC) family and genes involved in FA scavenging and lipid metabolism [50,51,76,79].”

    From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [76]

    The Introduction describes PPAR–RXR binding to PPREs as the general mechanism of PPAR action. Sections 5.5 and 8 report PPARα regulation of fatty-acid uptake genes and ABC-family genes, respectively. But the paper identifies a PPRE for only one fatty-acid transporter and says the mechanism of Abca1 upregulation is unclear, so it does not establish direct PPRE-mediated activation for all the gene groups named. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PPAR isomers are master regulators of hundreds of target genes involved in fatty acid oxidation, cholesterol and lipoprotein metabolism, lipid droplet formation, and inflammation.

    “PPAR isomers are master regulators of hundreds of target genes involved in FAO, cholesterol and lipoprotein metabolism, LD formation, and inflammation [75,76].”

    From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [76]

    The Introduction and Conclusion (pages unavailable) describe PPARα as a master regulator of hepatic metabolism, including fatty acid oxidation, lipoprotein and cholesterol metabolism, and inflammation. Section 5.6 links PPARα to lipid-droplet proteins. However, the paper focuses on PPARα rather than establishing the claim for all PPAR subtypes, and it describes a large number of target genes without substantiating the specific count of hundreds. (LLM, conf=0.87)

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Authors
Rakhshandehroo, M., Knoch, B., Müller, M., & Kersten, S.
Affiliations
  • Wageningen University & Research (NL)
  • AgResearch (NZ)
Corresponding author
Kersten, Sander
ORCID
Venue
PPAR Research
Publisher
Wiley
Published
2010
Volume
2010
Pages
1-20
ISSN
  • 1687-4757 (ISSN-L)
  • 1687-4765
DOI
10.1155/2010/612089
PMC
PMC2948931
OpenAlex
W1974744093
Cited by
1,020
References
12
Citations by year
2026: 42 · 2025: 63 · 2024: 59 · 2023: 48 · 2022: 54 · 2021: 76 · 2020: 87 · 2019: 69 · 2018: 77 · 2017: 74 · 2016: 69 · 2015: 58 · 2014: 85 · 2013: 57 · 2012: 48
FWCI
19.16
Type
journal article
Language
en
Open access
Licence
Locations
  • PPAR Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Socio-Environmental Systems Modeling (acceptedVersion)
  • Research Online (University of Wollongong) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion)
  • UEA Digital Repository (University of East Anglia) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
AgResearch
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords
PPARα, target genes, gene expression regulation, lipid metabolism, fibrates, fatty acid activation, liver, energy homeostasis, inflammation

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