Bioactive lipids and the gut-brain axis: Diet as a modulator of bioactivity and diversity of lipids in the brain

Abstract

The brain is highly rich in lipids, which accounts for roughly 50% of its dry weight. The brain lipidome, generally characterized over half a century ago, is comprised of thousands of biochemical structures expressed differentially as a function of brain region, structure, cell type and subcellular compartment. Lipids play diverse structural and functional roles in the brain, not only due to their chemical diversity but also due to the unique hydrophobic environment that they create. This lipophilic milieu promotes interactions involving reactive oxygen and nitrogen species that may not occur, at least at a similar extent, in aqueous environments. In the present chapter, we have focused on 3 distinct types of bioactive lipids and the roles played in brain physiology and pathology: nitrated fatty acids, cholesterol and endocannabinoids. These lipids are diverse in origin and bioactivity: (1) nitrated fatty acids result from biochemical modification of dietary fatty acids by nutrients and are proposed to play diverse physiological roles, namely by modulating NF-kB and Nfr2-dependent signaling cascades and post-translational modification of proteins. Produced in the gastric compartment, they are absorbed into circulation and can cross the blood-brain barrier, providing a new route for the interaction between the gastrointestinal tract and the brain; (2) cholesterol, synthetized de novo in the brain, not only regulates the biophysical properties of cellular membranes, but can also physically interact with neurotransmitter receptors and other membrane proteins and enzymes such as those involved in the processing and trafficking of the amyloid precursor protein (APP) and Aß peptide; (3) endocannabinoids, a class of neuromodulators derived from fatty acids that are synthetized and released upon demand and incite cellular responses by binding to specific membrane receptors. Being one of the most important and adjustable determinants of human health, our goal is to highlight the impact of diet on the bioactivity of lipids in the brain, discussing novel and provocative findings that advocate that lipids may modulate the gut-brain axis and therefore higher cortical functions such as motor function, learning and memory.