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Review
. 2013 Jan;88(1):43-7.
doi: 10.1016/j.plefa.2012.03.008. Epub 2012 Apr 18.

Membrane lipid raft organization is uniquely modified by n-3 polyunsaturated fatty acids

Harmony F Turk  1 , Robert S Chapkin
Affiliations
Review

Membrane lipid raft organization is uniquely modified by n-3 polyunsaturated fatty acids

Harmony F Turk et al. Prostaglandins Leukot Essent Fatty Acids. 2013 Jan.

Abstract

Fish oil, enriched in bioactive n-3 polyunsaturated fatty acids (PUFA), has been shown to play a role in prevention of colon cancer. The effects of n-3 PUFA are pleiotropic and multifaceted, resulting in an incomplete understanding of their molecular mechanisms of action. Here, we focus on a highly conserved mechanism of n-3 PUFA, which is the alteration of the organization of the plasma membrane. We highlight recent work demonstrating that enrichment of n-3 PUFA in the plasma membrane alters the lateral organization of membrane signaling assemblies (i.e. lipid rafts). This mechanism is central for n-3 PUFA regulation of downstream signaling, T-cell activation, transcriptional activation, and cytokine secretion. We conclude that these studies provide strong evidence for a predominant mechanism by which n-3 PUFA function in colon cancer prevention.

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Figures

Fig. 1
Fig. 1. Putative model for the effect of n-3 PUFA on lipid rafts
Lipid rafts are nanoscale regions of the plasma membrane, enriched in cholesterol, sphingomyelin, and phospholipids containing saturated acyl chains. Both transmembrane and peripheral membrane proteins can be localized to lipid rafts. Upon treatment with a combination of n-3 PUFA or DHA alone, these PUFA are incorporated into phospholipids which are inserted into both raft and non-raft regions of the plasma membrane. This results in enhanced clustering of lipid raft regions, which are depleted of cholesterol and sphingomyelin. Additionally, many lipid raft associated proteins “mislocalize” to the bulk membrane domain. This results in a suppression of lipid raft mediated processes, including T-cell activation and downstream signal transduction.
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