July 14, 2020

New tools to study bioactive lipids

Vanderbilt researchers have identified and characterized inhibitors of an enzyme that synthesizes lipid signaling molecules with roles in energy balance, inflammation and addiction.

NAEs are bioactive lipid molecules that appear to play roles in energy balance, inflammation, stress responses and addiction. How NAE levels are regulated and their precise contributions to biological processes remain poorly understood.

To develop tools to explore NAE function, Sean Davies, PhD, and colleagues screened a library of experimental compounds for inhibitors of NAPE-PLD, the enzyme that catalyzes the final step in NAE biosynthesis.

The researchers identified 14 inhibitors and further studied the two most potent compounds. They demonstrated that the compounds, dichlorophenes, were selective for and inhibited the NAPE-PLD enzyme in cultured human cells. They also identified the key chemical parts of the compounds required for NAPE-PLD inhibition.

The findings, reported in the Journal of Biological Chemistry, identify tools for studying NAE function and lay the groundwork for the development of therapies for clinical conditions including obesity, inflammation, chronic pain and addiction.

This research was supported by a Discovery Grant from the Vanderbilt Diabetes Center and by grants from the National Institutes of Health (DK105847, GM065086).