Peroxisome proliferator-activated receptor alpha and gamma agonists upregulate human macrophage lipoprotein lipase expression.
Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors which mediate pleiotropic effects including regulation of genes involved in lipid metabolism and control of inflammation. In the present study, we measured the in vitro effects of PPAR alpha and gamma ligands on macrophage lipoprotein lipase (LPL) expression. Human monocyte-derived macrophages (MDM) were cultured for 1-3 days in the presence of PPAR alpha and gamma ligands. At the end of these incubation periods, extracellular LPL immunoreactive mass/activity and LPL mRNA levels were measured. Incubation of human MDM with PPAR alpha and gamma ligands stimulated, in a time- and dose-dependent manner, human MDM LPL mass and activity. These agents also significantly increased macrophage LPL mRNA expression. In THP-1 cells treated with PPAR alpha and gamma ligands, enhanced nuclear protein binding to the peroxisome proliferator responsive element (PPRE) of the human LPL promoter was observed. Furthermore, in these cells, a decreased rate of decay of LPL mRNA was documented. Overall, these results demonstrate that PPAR alpha and gamma activators increase macrophage LPL secretion. Given the proatherogenic effect of vascular wall LPL, better understanding of the role of PPARs in the regulation of macrophage LPL expression could lead to the development of new approaches in the prevention and treatment of atherosclerosis.
CHUM Research Centre, Notre-Dame Hospital, Department of Biomedical Sciences, University of Montreal, Que., Canada.
Ling
L
Li
Marie-Claude
MC
Beauchamp
Geneviève
G
Renier
D001483:Base Sequence; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008071:Lipoprotein Lipase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D018160:Receptors, Cytoplasmic and Nuclear; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000494:pharmacology*; D015533:Transcriptional Activation; D015854:Up-Regulation
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D008071:Lipoprotein Lipase