Conjugated Linoleic Acid and Brain Metabolism: A Possible Anti-Neuroinflammatory Role Mediated by PPARα Activation

Abstract

Fatty acids play a crucial role in the brain as specific receptor ligands and as precursors of bioactive metabolites. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid (LA, 18:2 n-6) present in meat and dairy products of ruminants and synthesized endogenously in non-ruminants and humans, has been shown to possess different nutritional properties associated with health benefits. Its ability to bind to peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor key regulator of fatty acid metabolism and inflammatory responses, partly mediates these beneficial effects. CLA is incorporated and metabolized into brain tissue where induces the biosynthesis of endogenous PPARα ligands palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), likely through a positive feedback mechanism where PPARα activation sustains its own cellular effects through ligand biosynthesis. In addition to PPARα, PEA and OEA may as well bind to other receptors such as TRPV1, further extending CLA own anti-neuroinflammatory actions. Future studies are needed to investigate whether dietary CLA may exert anti-inflammatory activity, particularly in the setting of neurodegenerative diseases and neuropsychiatric disorders with a neuroinflammatory basis.

Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions

“…CLA is able to cross the blood-brain barrier and be incorporated and metabolized in the brain, where it plays different roles [180,181]. Peculiarly, CLA has been shown to induce the biosynthesis of endogenous PPAR-α ligands, PEA and OEA, likely through a positive feedback mechanism where PPAR-α activation sustains its own cellular effects through ligand biosynthesis [182]. In addition to PPAR-α, PEA and OEA can activate, indirectly or directly, other receptors such as transient receptor potential vanilloid 1 (TRPV1) [183,184], which are also implicated in metabolism regulation and anti-inflammatory activity [185].…”

Bioactivities, physicochemical parameters and GC/MS profiling of the fixed oil of Cucumis melo L seeds: A focus on anti-inflammatory, immunomodulatory, and antimicrobial activities

“…This activity could be due to the presence of a wide range of phytoconstituents in petroleum ether extract of Cucumis melo seeds such as terpenoids, sesquiterpenes, oxygenated and unoxygenated hydrocarbons, as well as unsaturated and saturated fatty acids which have been reported to exhibit anti-inflammatory activity (40). In addition, linoleic acid, the major fatty acid in the oil of Cucumis melo seeds, is reported to possess potent anti-inflammatory and antimicrobial activities (41,42). Moreover, alphatocopherol has been shown a potent anti-inflammatory activity (43).…”

Fatty Acid Metabolism and Derived-Mediators Distinctive of PPAR-α Activation in Obese Subjects Post Bariatric Surgery

“…The reduction of OEA at 6 Post may be ascribed to the minor induction of PPAR-α by the lower NEFA release from adipose tissue. It would be interesting to envisage a strategy to induce PPAR-α at 6 Post by nutritional [53] or pharmacological [54] treatments to evaluate whether OEA and 22:6-n3 levels will return to the high values found at 1 Post and further positively influence lipid and energy metabolism and perhaps reduce relapse incidence (Figure 6). levels will return to the high values found at 1 Post and further positively influence lipid and energy metabolism and perhaps reduce relapse incidence (Figure 6).…”