Docosahexaenoic acid (DHA) (DHA)

Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid that serves as a primary structural component of the human brain, cerebral cortex, retina, and sperm [1, 3]. Although it is a lipid molecule rather than a protein target, DHA exerts significant biological effects by acting as an endogenous ligand for various receptors, including the G protein-coupled receptor FFAR4 (GPR120) and nuclear receptors such as Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma) [2]. It is essential for normal neurological development and the maintenance of cognitive function throughout life, with its deficiency linked to neurodegenerative and psychiatric disorders [3]. DHA also possesses potent anti-inflammatory properties, primarily by serving as a precursor for specialized pro-resolving mediators (SPMs) like resolvins, protectins, and maresins [4]. Clinically, DHA is utilized in purified pharmaceutical forms or as a dietary supplement to treat severe hypertriglyceridemia and to support cardiovascular and prenatal health [5, 7]. Its unique chemical structure, containing six double bonds, allows it to modulate the biophysical properties of cell membranes, thereby influencing the function of membrane-bound proteins such as ion channels and rhodopsin [6].

Other names

Cervonic acid22:6n-3all-cis-docosa-4,7,10,13,16,19-hexaenoic acidDoconexent

DHA acts as an agonist for the G protein-coupled receptor FFAR4 (GPR120) and nuclear receptors like PPAR-gamma, which mediates anti-inflammatory and insulin-sensitizing effects [2]. It also serves as a substrate for the enzymatic synthesis of specialized pro-resolving mediators (SPMs), such as the D-series resolvins, which actively promote the resolution of inflammation [4]. Additionally, DHA is incorporated into phospholipid bilayers, where it increases membrane fluidity and modulates the activity of membrane-associated signaling proteins and ion channels [1, 6].