New insights into the role of fatty acids in the pathogenesis and resolution of inflammatory bowel disease

Abstract

Dietary and endogenously modified lipids modulate inflammation by functioning as intra- and intercellular signaling molecules. Proinflammatory lipid mediators such as the eicosanoids compete against the signaling actions of newly discovered modified fatty acids that act to resolve inflammation. In inflammatory bowel disease, multiple aberrancies in lipid metabolism have been discovered, which shed further light on the pathogenesis of intestinal inflammation. Mechanisms by which lipids modulate inflammation, abnormalities of lipid metabolism in the setting of inflammatory bowel disease, and potential therapeutic application of lipid derivatives in this setting are discussed.

FIGURE 1

Fatty acid nomenclature and structures. The nomenclature used to describe fatty acids has evolved to such an extent that multiple conventions are used in the literature. Common names, IUPAC nomenclature, informal denotation, and structures are defined for the fatty acids described herein.

FIGURE 2

Eicosanoid formation. During host immune responses, arachidonic acid is hydrolyzed from membrane phospholipids and is converted to multiple oxidized fatty acid metabolites via enzymatic and autocatalytic mechanisms. In general, eicosanoids mediate proinflammatory cell signaling pathways and are involved in the pathogenesis of IBD.

FIGURE 3

Antiinflammatory lipid mediators. Recent advances in inflammatory and lipid research have identified promising lipid mediators in vivo that appear to resolve inflammation, including nitrated fatty acids, resolvins, and lipoxins, and electrophilic oxo-fatty acid derivatives (EFOX).