Conjugated Linoleic Acid Isomers Reduce Cholesterol Accumulation in Acetylated LDL‐Induced Mouse RAW264.7 Macrophage‐Derived Foam Cells

Abstract

Synthetic activators of peroxisome proliferator-activated receptors (PPAR)-alpha and -gamma are capable of reducing macrophage foam cell cholesterol accumulation through the activation of genes involved in cholesterol homeostasis. Since conjugated linoleic acids (CLA) were also demonstrated to activate PPARalpha and PPARgamma in vivo and in vitro, we tested the hypothesis that CLA are also capable of reducing macrophage foam cell cholesterol accumulation. Thus, mouse RAW264.7 macrophage-derived foam cells were treated with CLA isomers, c9t11-CLA and t10c12-CLA, and linoleic acid (LA), as reference fatty acid, and analyzed for the concentrations of free and esterified cholesterol, cholesterol efflux and expression of genes involved in cholesterol homeostasis (CD36, ABCA1, LXRalpha, NPC-1, and NPC-2). Treatment with c9t11-CLA and t10c12-CLA, but not LA, lowered cholesterol accumulation, stimulated acceptor-dependent cholesterol efflux, and increased relative mRNA concentrations of CD36, ABCA1, LXRalpha, NPC-1, and NPC-2 (P < 0.05). In conclusion, the present study showed that CLA isomers reduce cholesterol accumulation in RAW264.7 macrophage-derived foam cells presumably by enhancing lipid acceptor-dependent cholesterol efflux.

The role of ruminant trans fat as a potential nutraceutical in the prevention of cardiovascular disease

“…In addition to PPAR-α, immunohistochemical staining of aortic vessels have shown an increased expression of PPAR-γ in c9,t11-CLA supplemented animals compared to controls (Toomey et al, 2003). Consistent with this, treatment with c9,t11-CLA in-vitro results in augmented acceptor-dependent cholesterol efflux from macrophage-derived foam cells and increased mRNA expression of genes involved in macrophage cholesterol efflux (Ringseis, Wen, Saal, & Eder, 2008). CLA has also been shown to suppress the production of pro-inflammatory cytokines (such as TNF-α), as well as interferon-γ induced cyclooxygenase-2 activity in mouse and human macrophages, both of which are considered characteristic changes of a PPAR-agonist treatment (Iwakiri, Sampson, & Allen, 2002;Stachowska et al, 2009;Yu, Correll, & Vanden Heuvel, 2002).…”

Attenuation of inflammatory response phenomena in periparturient dairy cows by the administration of an ω3 rumen protected supplement containing vitamin E

“…The issue still remains relevant in the management of dairy cows, therefore additional tools able to modulate inflammatory response, avoiding negative aspects and keeping positive ones, are needed. In this respect, potential candidates might be the conjugated linoleic acid (Butz et al 2007;Ringseis et al 2008), phytoextracts (Choi et al, 2003;, and polyunsaturated fatty acids (Calder, 2006a;Ballou et al, 2009), in particular the long chain ω3.…”

Effects of dietary conjugated linoleic acid on cytotoxicity of peripheral blood lymphocytes in piglets

“…The deposition of CLA in the immune cell membrane may change fatty acids composition, protein distribution, and conformation of the immune cell membrane and influenced activation of receptor molecules on the cell membrane, cellular signal transduction, and immune function (Ringseis et al 2008;Kim et al 2010;Hsu and Ip 2011). In line with this idea, we detected the effects of dietary CLA on proximal signal transduction of peripheral blood lymphocytes of piglets.…”