Polyunsaturated Fatty Acids: Conversion to Lipid Mediators, Roles in Inflammatory Diseases and Dietary Sources

Abstract

Polyunsaturated fatty acids (PUFAs) are important components of the diet of mammals. Their role was first established when the essential fatty acids (EFAs) linoleic acid and α-linolenic acid were discovered nearly a century ago. However, most of the biochemical and physiological actions of PUFAs rely on their conversion to 20C or 22C acids and subsequent metabolism to lipid mediators. As a generalisation, lipid mediators formed from n-6 PUFAs are pro-inflammatory while those from n-3 PUFAs are anti-inflammatory or neutral. Apart from the actions of the classic eicosanoids or docosanoids, many newly discovered compounds are described as Specialised Pro-resolving Mediators (SPMs) which have been proposed to have a role in resolving inflammatory conditions such as infections and preventing them from becoming chronic. In addition, a large group of molecules, termed isoprostanes, can be generated by free radical reactions and these too have powerful properties towards inflammation. The ultimate source of n-3 and n-6 PUFAs are photosynthetic organisms which contain Δ-12 and Δ-15 desaturases, which are almost exclusively absent from animals. Moreover, the EFAs consumed from plant food are in competition with each other for conversion to lipid mediators. Thus, the relative amounts of n-3 and n-6 PUFAs in the diet are important. Furthermore, the conversion of the EFAs to 20C and 22C PUFAs in mammals is rather poor. Thus, there has been much interest recently in the use of algae, many of which make substantial quantities of long-chain PUFAs or in manipulating oil crops to make such acids. This is especially important because fish oils, which are their main source in human diets, are becoming limited. In this review, the metabolic conversion of PUFAs into different lipid mediators is described. Then, the biological roles and molecular mechanisms of such mediators in inflammatory diseases are outlined. Finally, natural sources of PUFAs (including 20 or 22 carbon compounds) are detailed, as well as recent efforts to increase their production.

The association between n‐3 polyunsaturated fatty acid intakes and asthma in US children and adolescents: A cross‐sectional study from NHANES

“…29 In the case of asthma, replacing arachidonic acid (AA) with EPA and DHA is effective in reducing the synthesis of prostaglandins and leukotrienes, thereby reducing the inflammatory response. [30][31][32] Moreover, n-3 PUFAs can produce various anti-inflammatory metabolites, such as D-series catabolites and E-series protectors, which can exert powerful anti-inflammatory effects and may improve asthma symptoms and promote bronchodilation. 33,34 N-3 PUFAs play an important role in controlling inflammation and managing asthma by regulating cell membrane structure, inhibiting the synthesis of inflammatory mediators, and generating anti-inflammatory metabolites.…”

“…The n‐3 PUFAs mainly include DHA and EPA, which are naturally present in fish oil 29 . In the case of asthma, replacing arachidonic acid (AA) with EPA and DHA is effective in reducing the synthesis of prostaglandins and leukotrienes, thereby reducing the inflammatory response 30–32 . Moreover, n‐3 PUFAs can produce various anti‐inflammatory metabolites, such as D‐series catabolites and E‐series protectors, which can exert powerful anti‐inflammatory effects and may improve asthma symptoms and promote bronchodilation 33,34 .…”

Lipoxygenases at the Intersection of Infection and Carcinogenesis

“…Over time, various isoforms of this enzyme have been discovered, each bearing unique characteristics. Following the comprehensive sequencing of the human genome, six distinct functional lipoxygenase isoform genes were identified: ALOX15, ALOX15B, ALOX12, ALOX12B, ALOX5, and ALOXE3 [71,72].…”

Elongation capacity of polyunsaturated fatty acids in the annelidPlatynereis dumerilii

“…LC-PUFA are precursors of signalling molecules termed eicosanoids, which participate in immune responses and inflammation regulation (Dyall et al 2022). Generally, ARA-derived eicosanoids have pro-inflammatory properties, whereas those from EPA and DHA are anti-inflammatory, playing roles in immune regulation and contributing to cardiovascular health (Lee et al 2009; Swanson et al 2012; Manson et al 2019; Schulze et al 2020; Harwood, 2023). Additionally, DHA, particularly abundant in brain and retina cell membranes, contributes to neural development and function, supporting cognitive processes and visual acuity (Jeffrey et al 2001; Janssen et al 2014; Lauritzen et al 2016).…”