Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver.
Echium oil (EO), which is enriched in 18:4 n-3, the immediate product of fatty acid desaturase 2 (FADS2) desaturation of 18:3 n-3, is as atheroprotective as fish oil (FO). The objective of this study was to determine whether botanical oils enriched in the FADS2 products 18:3 n-6 versus 18:4 n-3 are equally atheroprotective. LDL receptor KO mice were fed one of four atherogenic diets containing 0.2% cholesterol and 10% calories as palm oil (PO) plus 10% calories as: 1) PO; 2) borage oil (BO; 18:3 n-6 enriched); 3) EO (18:4 n-3 enriched); or 4) FO for 16 weeks. Mice fed BO, EO, and FO versus PO had significantly lower plasma total and VLDL cholesterol concentrations; hepatic neutral lipid content and inflammation, aortic CE content, aortic root intimal area and macrophage content; and peritoneal macrophage inflammation, CE content, and ex vivo chemotaxis. Atheromas lacked oxidized CEs despite abundant generation of macrophage 12/15 lipooxygenase-derived metabolites. We conclude that botanical oils enriched in 18:3 n-6 and 18:4 n-3 PUFAs beyond the rate-limiting FADS2 enzyme are equally effective in preventing atherosclerosis and hepatosteatosis compared with saturated/monounsaturated fat due to cellular enrichment of ≥20 PUFAs, reduced plasma VLDL, and attenuated macrophage inflammation.
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.
Elena
E
Boudyguina
Departments of Internal Medicine-Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Xuewei
X
Zhu
Departments of Internal Medicine-Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Lulu
L
Shen
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045.
Patrick M
PM
Hutchins
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045.
Robert M
RM
Barkley
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045.
Robert C
RC
Murphy
Departments of Internal Medicine-Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157 Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157.
John S
JS
Parks
D000818:Animals; D050197:Atherosclerosis / Q000178:diet therapy* / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000097:blood; D004036:Diet, Atherogenic; D036661:Echium / Q000737:chemistry; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000737:chemistry; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000737:chemistry; D005234:Fatty Liver / Q000178:diet therapy; D005395:Fish Oils / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000073878:Palm Oil; D010938:Plant Oils / Q000008:administration & dosage* / Q000737:chemistry; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000008:administration & dosage / Q000737:chemistry
D015243:Cholesterol, VLDL; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D010938:Plant Oils; D011973:Receptors, LDL; D000073878:Palm Oil; D017965:gamma-Linolenic Acid; D044943:Fatty Acid Desaturases; C079363:borage oil
fatty acid desaturase 2; fatty acid/metabolism; inflammation; lipoproteins/metabolism; macrophages/monocytes; mass spectrometry; very low density lipoprotein