Cited by 317Peroxisome Proliferator-Activated ReceptorsCholesterol and Lipid MetabolismParaoxonase enzyme and polymorphisms

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Activation of PPARδ alters lipid metabolism in db/db mice

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Leibowitz, Mark D., Fiévet, Catherine, Hennuyer, Nathalie, Peinado-Onsurbe, Julia, Duez, Hélène, Berger, Joel, Cullinan, Catherine A., Sparrow, Carl P., Baffic, Joanne, Berger, Gregory D., Santini, Conrad, Marquis, Robert W., Tolman, Richard L., Smith, Roy G., Moller, David E., Auwerx, Johan·2000·FEBS Letters

DOI 10.1016/s0014-5793(00)01554-4

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Abstract

Peroxisome proliferator‐activated receptors (PPARs) are nuclear receptors, which heterodimerize with the retinoid X receptor and bind to peroxisome proliferator response elements in the promoters of regulated genes. Despite the wealth of information available on the function of PPARα and PPARγ, relatively little is known about the most widely expressed PPAR subtype, PPARδ. Here we show that treatment of insulin resistant db/db mice with the PPARδ agonist L‐165 041, at doses that had no effect on either glucose or triglycerides, raised total plasma cholesterol concentrations. The increased cholesterol was primarily associated with high density lipoprotein (HDL) particles, as shown by fast protein liquid chromatography analysis. These data were corroborated by the chemical analysis of the lipoproteins isolated by ultracentrifugation, demonstrating that treatment with L‐165 041 produced an increase in circulating HDL without major changes in very low or low density lipoproteins. White adipose tissue lipoprotein lipase activity was reduced following treatment with the PPARδ ligand, but was increased by a PPARγ agonist. These data suggest both that PPARδ is involved in the regulation of cholesterol metabolism in db/db mice and that PPARδ ligands could potentially have therapeutic value.

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Authors: Leibowitz, M. D., Fiévet, C., Hennuyer, N., Peinado-Onsurbe, J., Duez, H., Berger, J., Cullinan, C. A., Sparrow, C. P., Baffic, J., Berger, G. D., Santini, C., Marquis, R. W., Tolman, R. L., Smith, R. G., Moller, D. E., & Auwerx, J.
Affiliations: Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Inserm (FR)
Corresponding author: Leibowitz, Mark D.
ORCID: Hennuyer, Nathalie
Duez, Hélène
Santini, Conrad
Moller, David E.
Auwerx, Johan
Venue: FEBS Letters
Publisher: Wiley
Published: 2000-05-12
Volume: 473
Issue: 3
Pages: 333-336
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/s0014-5793(00)01554-4
OpenAlex: W2024254257
Cited by: 308
References: 26
Citations by year: 2025: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 9 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 13 · 2012: 8
FWCI: 7.23
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: FEBS Letters (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords: PPARδ, db/db mice, type 2 diabetes, insulin resistance, HDL cholesterol, serum cholesterol, lipoprotein lipase, white adipose tissue, PPARγ agonists, lipid metabolism, nuclear receptors
MeSH terms: Acetates, Adipose Tissue, Animals, Blood Glucose, Cholesterol, Chromatography, Liquid, DNA-Binding Proteins, Ligands, Lipids, Lipoprotein Lipase, Lipoproteins, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Phenols, Phenoxyacetates, Transcription Factors, Triglycerides, Ultracentrifugation, Receptors, Cytoplasmic and Nuclear, Mice

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Activation of PPARδ alters lipid metabolism in db/db mice

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