Transcriptional control of triglyceride metabolism: fibrates and fatty acids change the expression of the LPL and apo C-III genes by activating the nuclear receptor PPAR.
The development of atherosclerosis is often associated with altered concentrations of systemic lipoproteins, which are determined by the concentration and/or activity of three groups of different proteins, i.e. apolipoproteins (apo), enzymes, and receptors. The effects of diet or therapeutic interventions on lipid metabolism are mediated by changes in activity or concentrations of these three components. Fibrates have been shown to activate nuclear receptors belonging to the steroid hormone receptor super-family, termed peroxisome proliferator activated receptor (PPAR). These activated PPARs are potent transcription factors which influence the expression of several target genes implicated in lipoprotein homeostasis, e.g. LPL, apo C-III and apo A-1. Fibrates decrease apo C-III transcription and increase LPL production via these PPARs resulting in a profound hypotriglyceridaemic effect. Apolipoproteins and enzymes are important in governing lipid metabolism, thus therapeutically altering the expression of these genes constitutes an efficient therapeutic option.
Auwerx
J
J
INSERM U325, Département d'Athérosclérose, Institut Pasteur, Lille, France.
Schoonjans
K
K
Fruchart
J C
JC
Staels
B
B
D000818:Animals; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics* / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000378:metabolism / Q000517:prevention & control; D005227:Fatty Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014280:Triglycerides / Q000235:genetics* / Q000378:metabolism*
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D002087:Butyrates; D005227:Fatty Acids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D008071:Lipoprotein Lipase