Activation of PPARdelta alters lipid metabolism in db/db mice.
| Title: | Activation of PPARdelta alters lipid metabolism in db/db mice. |
|---|---|
| Authors: | Leibowitz MD; Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, NJ 07065, USA. mleibowitz@ligand.com; Fiévet C; Hennuyer N; Peinado-Onsurbe J; Duez H; Bergera J; Cullinan CA; Sparrow CP; Baffic J; Berger GD; Santini C; Marquis RW; Tolman RL; Smith RG; Moller DE; Auwerx J |
| Source: | FEBS letters [FEBS Lett] 2000 May 19; Vol. 473 (3), pp. 333-6. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: John Wiley & Sons Ltd Country of Publication: England NLM ID: 0155157 Publication Model: Print Cited Medium: Print ISSN: 0014-5793 (Print) Linking ISSN: 00145793 NLM ISO Abbreviation: FEBS Lett Subsets: MEDLINE |
| Imprint Name(s): | Publication: Jan. 2016- : West Sussex : John Wiley & Sons Ltd.; Original Publication: Amsterdam, North-Holland on behalf of the Federation of European Biochemical Societies. |
| MeSH Terms: | DNA-Binding Proteins/*metabolism ; Lipids/*blood ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Transcription Factors/*metabolism; Acetates/pharmacology ; Adipose Tissue/metabolism ; Blood Glucose/metabolism ; Cholesterol/chemistry ; Cholesterol/metabolism ; DNA-Binding Proteins/chemistry ; Lipoprotein Lipase/metabolism ; Lipoproteins/chemistry ; Lipoproteins/metabolism ; Phenols/pharmacology ; Receptors, Cytoplasmic and Nuclear/chemistry ; Transcription Factors/chemistry ; Triglycerides/blood ; Animals ; Chromatography, Liquid ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Phenoxyacetates ; Ultracentrifugation |
| 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 PPARalpha and PPARgamma, relatively little is known about the most widely expressed PPAR subtype, PPARdelta. Here we show that treatment of insulin resistant db/db mice with the PPARdelta agonist L-165041, 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-165041 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 PPARdelta ligand, but was increased by a PPARgamma agonist. These data suggest both that PPARdelta is involved in the regulation of cholesterol metabolism in db/db mice and that PPARdelta ligands could potentially have therapeutic value. |
| Substance Nomenclature: | 0 (4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid); 0 (Acetates); 0 (Blood Glucose); 0 (DNA-Binding Proteins); 0 (Ligands); 0 (Lipids); 0 (Lipoproteins); 0 (Phenols); 0 (Phenoxyacetates); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Transcription Factors); 0 (Triglycerides); 97C5T2UQ7J (Cholesterol); EC 3.1.1.34 (Lipoprotein Lipase) |
| Entry Date(s): | Date Created: 20000520 Date Completed: 20000707 Latest Revision: 20190621 |
| Update Code: | 20260130 |
| DOI: | 10.1016/s0014-5793(00)01554-4 |
| PMID: | 10818235 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't