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.

Keywords: brain; conjugated linoleic acid; lipid nutrition; neuroinflammation; peroxisome proliferator-activated receptor α.

FIGURE 1

Concentrations of palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) analyzed by LC-MS as described in (Piras et al., 2015), in rat horizontal slices containing the midbrain incubated for 1 h with 100 µM of synthetic and endogenous ligands of PPARα or their vehicle: agonist WY14643 (WY), oleic acid (18:1), palmitic acid (16:0), linoleic acid (18:2), c9-t11, t10-c12, and a mixture of both CLA isomers (CLA), or PPARα antagonist (MK886). Error bars represent SD; n = 6. * denote significant differences (p < 0.05), vs. control (one-way ANOVA).

FIGURE 2

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) levels analyzed by LC-MS as described in (Piras et al., 2015), in the hypothalamus of gavage-treated mice, fed a standard diet, with a single dose (90 µg/10 g of body weight) of CLA (CLA) or olive oil (Ctrl). N = 6. Error bars represent SEM; * denote significant differences (p < 0.05) vs. control (one-way ANOVA).