A conjugated linoleic acid-enriched beef diet attenuates lipopolysaccharide-induced inflammation in mice in part through PPARgamma-mediated suppression of toll-like receptor 4.
Conjugated linoleic acid (CLA) is a PUFA found in beef and dairy products that has immunoregulatory properties. The level of CLA in beef can be enhanced by feeding cattle fresh grass rather than concentrates. This study determined the effect of feeding a high-CLA beef diet on inflammation in an in vivo model of septic shock. Mice were fed a high-CLA beef (4.3% total fatty acid composition) or low-CLA beef diet (0.84% total fatty acid composition) for 6 wk. Lipopolysaccharide (LPS; 3 microg) or sterile PBS was injected i.v. and serum was harvested 6 h after injection. Serum interleukin (IL)-1beta, IL-12p70, IL-12p40, and interferon-gamma concentrations were significantly reduced in response to the LPS challenge in the high-CLA beef diet group. Bone marrow-derived dendritic cells (BMDC) from the high-CLA beef diet group had significantly less IL-12 and more IL-10 in response to ex vivo LPS stimulation. Furthermore, toll-like receptor 4 (TLR4) and CD14 protein and mRNA expression on BMDC was significantly attenuated in the high-CLA compared with the low-CLA beef diet group. Complimentary in vitro experiments to determine the specificity of the effect showed that synthetic cis9, trans11-CLA suppressed surface expression of CD14 and TLR4 on BMDC. Treatment with the PPARgamma inhibitor GW9662 partially reversed TLR4 expression in immature BMDC. The results of this study demonstrate that feeding a diet enriched in high-beef CLA exerts profound antiinflammatory effects in vivo within the context of LPS-induced sepsis. In addition, downregulation of BMDC TLR4 is mediated through induction of PPARgamma.
UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
Clare M
CM
Reynolds
Eve
E
Draper
Brian
B
Keogh
Arman
A
Rahman
Aidan P
AP
Moloney
Kingston H G
KH
Mills
Christine E
CE
Loscher
Helen M
HM
Roche
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D002417:Cattle; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005514:Food Irradiation; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008460:Meat; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D018805:Sepsis / Q000517:prevention & control; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics*
D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D047495:PPAR gamma; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4