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Review
. 2013 Oct 22;14(10):21167-88.
doi: 10.3390/ijms141021167.

Dietary polyunsaturated fatty acids and inflammation: the role of phospholipid biosynthesis

William Raphael  1 , Lorraine M Sordillo
Affiliations
Review

Dietary polyunsaturated fatty acids and inflammation: the role of phospholipid biosynthesis

William Raphael et al. Int J Mol Sci. .

Abstract

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. Inflammation can be exacerbated with intake of certain dietary fatty acids, such as some ω-6 polyunsaturated fatty acids (PUFA), and subsequent incorporation into membrane phospholipids. Inflammation, however, can be resolved with ingestion of other fatty acids, such as ω-3 PUFA. The influence of dietary PUFA on phospholipid composition is influenced by factors that control phospholipid biosynthesis within cellular membranes, such as preferential incorporation of some fatty acids, competition between newly ingested PUFA and fatty acids released from stores such as adipose, and the impacts of carbohydrate metabolism and physiological state. The objective of this review is to explain these factors as potential obstacles to manipulating PUFA composition of tissue phospholipids by specific dietary fatty acids. A better understanding of the factors that influence how dietary fatty acids can be incorporated into phospholipids may lead to nutritional intervention strategies that optimize health.

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Figures

Figure 1
Figure 1
Phospholipids consist of glycerol, usually esterified to a saturated long chain fatty acid at sn-1 and to an unsaturated long chain fatty acid at sn-2, and to a phosphorylated head group at sn-3. This example is 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero- 3-phosphocholine.
Figure 2
Figure 2
Fatty acyl chains of phospholipids located within the membranes of cells and organelles may be enzymatically oxidized into lipid mediators. Examples of proinflammatory (orange), resolving (blue), and variable function (green) lipid mediators are illustrated by fatty acid substrate (yellow) and biosynthetic enzyme. *: aspirin acetylated; LA: linoleic acid; AA: arachidonic acid; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; COX: cyclooxygenase; Cyt-P450: cytochrome-P450 complex; HEPE: hydroxyeicosapentaenoic acid; HETE: hydroxyeicosatetraenoic acid; HODE: hydroxyoctadecadienoic acid; LOX: lipoxygenase; LT: leukotriene; LX: lipoxin; MaR: maresin; PG: prostaglandin; Rv: resolvin; PD: protectin; TX: thromboxane.
Figure 3
Figure 3
The utilization of long chain fatty acids for de novo phospholipid biosynthesis (Kennedy pathway, red arrows and boxes), post-synthetic modification of phospholipids by reacylation (Lands’ cycle, green arrow), and the metabolism of phospholipids to oxidized lipid mediators of inflammation (orange arrow and box) in critical cells during inflammatory responses, such as vascular endothelial cells and mononuclear leukocytes. Origins of fatty acid substrate addressed in this review are (solid blue arrows and boxes) adipose triacylglycerol-derived fatty acid 1, fatty acid synthesized de novo2, recently absorbed dietary fatty acid 3, and phospholipid-derived fatty acid, cleaved by phospholipases then recycled for phospholipid biosynthesis 4 (broken blue arrow).
Figure 4
Figure 4
Biosynthetic pathway of major phospholipids in vascular endothelial tissue and mononuclear leukocytes. Metabolites are boxed, enzymes are unboxed. Note that diacylglycerol is a substrate for both triacylglycerol and phospholipids. Key: ACSL: acyl CoA synthase (ligase); AGPAT: 1-acylglycerol-3-phosphoacyltransferase; CDP-choline: cytidine-diphosphate choline; CDS: cytidine-diphosphate diacylglycerol synthase; CL: cardiolipin; CCT: cytidine-triphosphate:phosphocholine cytidylyltransferase; DG: diacylglycerol; DGAT: diacylglycerol acyltransferase; GPAT: glycerol-3-phosphoacyltransferase; PA: phosphatidic acid; PC: phosphocholine; PE: phosphoethanolamine; PG: phosphoglycerol; PI: phosphoinositol; PPAP: phosphatidic acid phosphatase; PS: phosphoserine; TG: triacylglycerol.
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