In vivo activation of leukocyte GPR120/FFAR4 by PUFAs has minimal impact on atherosclerosis in LDL receptor knockout mice.
G protein-coupled receptor (GPR)120/FFA receptor (FFAR)4 (GPR120/FFAR4) activation by n-3 PUFAs attenuates inflammation, but its impact on atherosclerosis is unknown. We determined whether in vivo activation of leukocyte GPR120/FFAR4 by n-3 versus n-6 PUFAs is atheroprotective. Leukocyte GPR120/FFAR4 WT or KO mice in the LDL receptor KO background were generated by bone marrow transplantation. Mice were fed one of the four atherogenic diets containing 0.2% cholesterol and 10% calories as palm oil (PO) + 10% calories as: 1) PO, 2) fish oil (FO; 20:5 n-3 and 22:6 n-3 enriched), 3) echium oil (EO; 18:4 n-3 enriched), or 4) borage oil (BO; 18:3 n-6 enriched) for 16 weeks. Compared with PO, mice fed BO, EO, and FO had significantly reduced plasma cholesterol, TG, VLDL cholesterol, hepatic neutral lipid, and atherosclerosis that were equivalent for WT and KO mice. In BO-, EO-, and FO-fed mice, but not PO-fed mice, lack of leukocyte GPR120/FFAR4 resulted in neutrophilia, pro-inflammatory Ly6Chimonocytosis, increased aortic root monocyte recruitment, and increased hepatic inflammatory gene expression. In conclusion, leukocyte GPR120 expression has minimal effects on dietary PUFA-induced plasma lipid/lipoprotein reduction and atheroprotection, and there is no distinction between n-3 versus n-6 PUFAs in activating anti-inflammatory effects of leukocyte GPR120/FFAR4 in vivo.
Departments of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.|Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Swapnil V
SV
Shewale
Departments of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Amanda L
AL
Brown
Departments of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Xin
X
Bi
Departments of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Elena
E
Boudyguina
Departments of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Janet K
JK
Sawyer
Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Martha A
MA
Alexander-Miller
Departments of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157 jparks@wakehealth.edu.|Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157.
John S
JS
Parks
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D004036:Diet, Atherogenic; D015525:Fatty Acids, Omega-3 / Q000235:genetics / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
C498007:FFAR4 protein, mouse; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL; D002784:Cholesterol
G protein-coupled receptor 120/free fatty acid receptor 4; G proteins; fatty acid; inflammation; low density lipoprotein; macrophages/monocytes; omega-3 fatty acids; polyunsaturated fatty acids