Immuno‐Resolving Ability of Resolvins, Protectins, and Maresins Derived from Omega‐3 Fatty Acids in Metabolic Syndrome

Abstract

Omega‐3 fatty acid consumption has been suggested to be beneficial for the prevention of type 2 diabetes mellitus (T2DM). Its effects have been attributed to anti‐inflammatory activity, with the inhibition of arachidonic acid metabolism playing a central role. However, a more recent view is that omega‐3 fatty acids play an active role as the precursors of potent, specialized pro‐resolving mediators (SPMs), such as resolvins, protectins, and maresins. Docosahexaenoic acid (DHA)‐ and eicosapentaenoic‐acid‐derived SPMs are identified in the adipose tissue but the levels of certain SPMs (e.g., protectin D1) are markedly reduced with obesity, suggesting adipose SPM deficiency, potentially resulting in unresolved inflammation. Supplementation of the biosynthetic intermediates of SPM (e.g., 17‐hydroxy‐DHA) or omega‐3 fatty acids increases the level of adipose SPMs, reduces adipose inflammation (decrease in macrophage accumulation and change to less inflammatory macrophages), and enhances insulin sensitivity. The findings from studies using rodent obesity models must be translated to humans. It will be important to further elucidate the underlying mechanisms by which obesity reduces the levels of and the sensitivity to SPM in adipose tissues. This will enable the development of nutrition therapy to enhance the effects of omega‐3 fatty acids in the prevention and/or treatment of T2DM.

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

“…It can regulate proinflammatory cytokines, including NF-κB, IL-1β, IL-6, and TNF-α [ 61 ]. Resolvins are produced from DHA and EPA and are denoted as the D-series (RvD1–RvD6) and E-series (RvE1–RvE3), respectively, while certain isomers of RvDs termed aspirin-triggered resolvin Ds (AT-RvDs) require acetylated COX-2 in the presence of aspirin or other nonsteroid anti-inflammatory drugs for their synthesis [ 62 ]. Resolvins exhibit their proresolving effects through specific G-protein coupled receptors (GPR).…”

Lipid-Induced Mechanisms of Metabolic Syndrome

“…A balanced n-6 : n-3 PUFAs ratio (where 1 : 1 to 2 : 1 is optimal) is important for homeostasis and normal development throughout the lifespan. High n-6 PUFA intake in the Western diet increases the n-6 : n-3 ratio to a range from 10 : 1 to 20 : 1 and may play a role in the pathogenesis of MetS and related diseases [ 36 ]. The balance between n-3 PUFAs and n-6 PUFAs determines the path of inflammatory response.…”

“…Docosahexaenoic acid- and eicosapentaenoic acid-derived SPMs are identified in the adipose tissue. At the same time, the levels of certain SPMs are markedly reduced with obesity, suggesting adipose SPM deficiency, potentially resulting in unresolved inflammation [ 36 ].…”

“…Alteration in the metabolism of fatty acids affects the synthesis of eicosanoids and pro-resolving lipid mediators responsible for immune-metabolic homeostasis [ 30 – 33 ]. Recent studies have further elucidated the role of these metabolites in the contribution to the chronic, low-grade inflammatory state in MetS [ 34 – 36 ]. A comprehensive understanding of the importance of lipids in the pathogenesis of MetS contributes to the development of preventive and targeted lipid-correcting therapy.…”

Better prepare for the next one. Lifestyle lessons from the COVID-19 pandemic

“…Fatty acids of the omega 3 series, which are essential, are the precursors of many molecules, e.g. resolvins, proteins and maresins, that accelerate the resolution of inflammatory processes [11]. 3 Sedentary lifestyle, overweight/obesity, and metabolic diseases.…”