Mounting evidence indicates that saturated fatty acids amplify inflammation. Fatty acids can activate G-protein–coupled receptors and initiate the arachidonic acid cascade. This in turn leads to production of eicosanoids, lipid mediators of inflammation.
“Global lipid analysis is indispensable in quantitation of all products in the inflammatory cascade,” says Dr. Dennis. “One of the major achievements of the LIPID MAPS consortium is development of over 500 standards covering eight main lipid categories in plasma, as well as 150 authentic eicosanoid standards. Now we can follow production of eicosanoids in response to inflammatory stimuli and correlate the molecular profiles with physiological manifestations of inflammation.”
In the study of inflammation caused by Borrelia (an agent of Lyme disease), the team identified a number of unusual eicosanoids, including resolvins and protectins thought to help resolve inflammation.
“We are just beginning to explore ways to increase the levels of beneficial anti-inflammatory eicosanoids,” says Dr. Dennis. “By applying lipidomic tools to model systems we can follow eicosanoid fluxes in response to inflammatory stimuli. Then we overlay the effects of dietary supplements.”
While dietary fish oil, rich in omega-3 fatty acids, was long known to elicit anti-inflammatory effects, the exact mechanism of action was not understood. Using the comprehensive analysis of the whole lipid cascade, Dr. Dennis and colleagues were able to demonstrate the direct mechanistic effects of omega-3 fatty acids on the production of mediators.
“Current technological achievements in lipidomics offer incredible opportunities to understand diseases and then to find mechanisms to treat them,” explains Dr. Dennis. “Investigation of hyperalgesia, or hypersensitivity caused by previous trauma, such as a burn or mechanical injury, is an example of such lipidomic discovery.”
Peripheral injury generates eicosanoid “memory signatures” in neurons. A new discovery showed that hepoxilins, metabolites in these signatures, act on well-known receptors of calcium signaling. These findings now enable development of anti-inflammatory therapeutics targeting these receptors.