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  • Writer's pictureTravis Cesarone

Inactive endocannabinoidome resident targets PPARs in new discovery

Updated: Feb 3, 2023

N-stearoylethanolamine (NSE) is a lipid agent without a known mechanism of action. Recently, however, a small team of researchers from the National Academy of Science in Kyiv, Ukraine, found a new target for NSE.

Published in the journal, Heliyon by Cell Press, the Ukrainian research team analyzed NSE’s role in macrophages. Previous research noted the lipid upticks macrophage expression and other specific effects on the immune system. But the exact causative link between the lipid and the immune system was unknown.

What is NSE?

N-steroylethanolamine is a saturated fat, meaning it contains no double-bonded electron pairs. The straight-chain fatty acid shares parentage with the endocannabinoid anandamide (AEA.) Lipids such as NSE, AEA, and other relatives come from the same precursor known as N-acyl-phosphatidylethanolamine (NAE.) An enzyme known as NAPE-d reacts with NAE to produce anandamide, an unsaturated lipid.

The metabolic pathway produces other likewise, but anandamide exclusively targets the cannabinoid receptor, CB1. OEA and PEA are relatives that target a unique receptor known as peroxisome proliferator-activated receptor (PPAR) alpha.

NAEs, part of the endocannabidiome family

Oleoylethanolamide (OEA) is unsaturated like anandamide. Scientists identified OEA as a PPAR-a agonist by 2003. Two years later, Palmitoylethanolamide (PEA), a saturated relative, was found to agonize PPAR-a.

NSE is saturated like PEA and binds to PPAR-gamma, according to the Ukrainian study. The lipid, therefore, might have a role in insulin sensitivity and immune and gene regulation, among other benefits. Unlike anandamide, it is not a true endocannabinoid due to a lack of activity at cannabinoid receptors. NSE is, however, part of the larger endocannabidiome with its family members.

Clues in likewise PPAR therapy

NSE pancreas lipid levels and returns the liver to regular function, to name several of its PPAR-dependent mechanisms. The lipid protects cells from oxidative stress, increases insulin sensitivity, and regulates cholesterol ratio.

NSE significantly inhibits a major transcription factor known as NF-kB, which is responsible for significant inflammatory signals such as cytokine expression. NF-kB’s subunit, P65, expressed a particular response to PPAR-gamma. These interactions helped the researchers target NSE’s therapeutic potential as a PPAR-y agonist within the endocannabinoidome.

Let us know in the comments if you want to know more about PEA and the rest of the NAE family.

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