(PTFS15-01-26) Identification of Conjugated Linoleic Acid (CLA)-Derived N-acylethanolamine (CLEA) As Potential Mediator of CLA Anti-inflammatory Effect on Microglia

Monday, July 27, 2026

12:30 PM - 12:34 PM ET

Location: Prince George's Hall B-E (The Hub) - Poster Theater 1 / Poster Board Number: PT1-1

Presenting Author(s)

MM

Maria Elisabetta Murru, PhD

Assistant Professor (RTT)
University of Cagliari
Cagliari, Sardegna, Italy

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

CP

Clara Porcedda, PhD

University of Cagliari
Cagliari, Sardegna, Italy
Claudia Manca, PhD

Assistant Professor (RTD-B, tenure-track position in the Italian system)
University of Cagliari
CAGLIARI, Sardegna, Italy
GC

Gianfranca Carta, PhD (she/her/hers)

Associate Professor
University of Cagliari
Cagliari, Sardegna, Italy
MC

Monica Cabboi, PhD- expected 2027

University of Cagliari
Monserrato, Sardegna, Italy
CC

Claudia Cocco, MSC

University of Cagliari
Cagliari, Sardegna, Italy
CI

Claudio Intini, PhD

University of Cagliari
Cagliari, Sardegna, Italy
FP

Franca Piras, PhD

University of Cagliari
Cagliari, Sardegna, Italy
VS

Valeria Sogos, PhD

University of Cagliari
Cagliari, Sardegna, Italy
Sebastiano Banni, PhD (he/him/his)

full Professor
University of Cagliari
Monserrato, Sardegna, Italy

Disclosure(s):

Maria Elisabetta Murru, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Conjugated linoleic acid (CLA) comprises positional and geometric isomers of linoleic acid (LA) characterized by a conjugated double bond (CD) structure retained during metabolism. CLA exerts pleiotropic metabolic and anti-inflammatory effects, partly modulating bioactive N-acylethanolamines (NAE) biosynthesis. Although several fatty acids (FA) act as NAE precursors, no CLA-derived NAE has yet been identified. This preliminary study investigates whether CLA can serve as a substrate for the biosynthesis of the unrecognized conjugated-linoleoylethanolamide (CLEA) and further evaluates CLEA’s potential role in modulating neuroinflammatory responses in BV-2 microglial cells.

Methods: To establish a cellular model of neuroinflammation, following 48 hours of treatment with CLA or oleic acid (OA) (25 µM), and CLEA or OA-derived oleoylethanolamide (OEA) (0,25 µM), BV-2 cells were exposed to lipopolysaccharide (LPS). Total lipids were analyzed by DAD-HPLC and UHPLC-MS/MS for CLEA identification and quantification. mRNA expression and secretion of pro-inflammatory markers (CCL5, IL-1β, IL-6, iNOS) were assessed.

Results: UHPLC–MS/MS analysis of CLA and CLEA-treated cells identified a previously unreported molecule exhibiting a MRM transition of 324→62.1, analogous to LA-derived linoleoylethanolamide (LEA). Structural characterization discriminated a distinct LEA isomeric species, leading to the novel identification of a CLA-derived NAE (CLEA). DAD-HPLC analysis revealed a peculiar absorption maximum at 234 nm, consistent with a distinctive CD structure supporting structural derivation from CLA. Functionally, preliminary data indicate that CLEA attenuated LPS-induced microglial activation, demonstrating anti-inflammatory efficacy at concentrations approximately 100-fold lower than those required for CLA, with significant reductions in pro-inflammatory molecules at both gene and protein levels.

Conclusions: Our findings reveal a previously unrecognized metabolic fate of CLA and identify CLEA as a novel endogenous lipid mediator. The discovery of CLEA establishes, for the first time, a direct link between CLA and NAE biosynthesis, offering a new biochemical framework for understanding the anti-inflammatory effects of CLA in the central nervous system.

Funding Sources: Progetto PRIN-2022