Conjugated linoleic acids regulate triacylglycerol and cholesterol concentrations in macrophages/foam cells by the modulation of CD36 expression.
Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in food, e.g. linoleic acid and n-3 unsaturated fatty acids can modulate expression of CD36 on the macrophage surface. Conjugated linoleic acid isomers (CLA) that originate from the human diet, have demonstrated antiatherogenic properties in several experiments. Animal study evidenced that CLA could induce resolution of plaque by activation of peroxisome proliferator activated receptors and down-regulation of pro-inflammatory genes. Less unequivocal results were obtained in human studies (on the CLA effects on the inflammatory process). Therefore in this study we investigated the influence of CLA on CD36 expression and lipid accumulation in human macrophages. Macrophages were incubated with 30 μM cis-9,trans-11 CLA, trans-10,cis-12 CLA or linoleic acid for 48 h. After that, expression of CD36 as well as accumulation of lipids were measured by flow cytometry, microscopy and a spectroscopic method. We demonstrate that both cis-9,trans-11 C 18 : 2 CLA and linoleic acid slightly elevated expression of CD36, whereas second isomer — trans-10,cis-12 CLA — did not. Nevertheless, only trans-10,cis-12 CLA triggered delipidation of macrophages, that is decreased triacylglycerols concentration. Also in human adipocytes, trans-10,cis-12 CLA causes cell delipidation by reduction of PPAR receptor expression. We propose a similar mechanism for human macrophages/foam cells.
Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland. ewast@sci.pam.szczecin.pl
Ewa
E
Stachowska
Magdalena
M
Baskiewicz
Mariola
M
Marchlewicz
Katarzyna
K
Czupryńska
Mariusz
M
Kaczmarczyk
Barbara
B
Wiszniewska
Bogusław
B
Machaliński
Dariusz
D
Chlubek
D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D018613:Microscopy, Confocal; D014280:Triglycerides / Q000378:metabolism*
D018955:CD36 Antigens; D044243:Linoleic Acids, Conjugated; D014280:Triglycerides; D002784:Cholesterol