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Activation of PPARδ alters lipid metabolism in db/db mice
Author(s) -
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
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01554-4
Subject(s) - peroxisome proliferator activated receptor , endocrinology , medicine , receptor , agonist , lipid metabolism , nuclear receptor , biology , lipoprotein lipase , ppar agonist , lipoprotein , adipose tissue , metabolism , chemistry , cholesterol , biochemistry , transcription factor , gene
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.