Omega-6 fatty acids

Linoleic acid is the simplest omega-6 fatty acid that can generate longer n-6 polyunsaturated fatty acids such as eicosanoids, endocannabinoids and lipoxins by the insertion of additional double bonds during consecutive elongation and desaturation mechanisms. It gives rise to arachidonic acid (AA) via γ-linolenic acid (GLA, 18:3n-6) and dihomo-γ-linolenic acid (DGLA, 20:3n-6) and the same set of enzymes can also convert AA to EPA and DHA. The initial rate limiting desaturation of LA to GLA is catalysed by the enzyme delta-6-desaturase (FADS2) and elongation of GLA to DGLA by delta-5-desaturase (FADS1) generates AA. AA is also converted to 2-series prostaglandins (PGD2, PGE2, PGF2, PGI2) andthromboxanes (TXA2, TXB2) by COX-2 activity and 4-series leukotrienes (LTA4, LTB4, LTC4, LTD4, LTE4) by 5-LOX activity. Resulting lipid signalling molecules have various pro-inflammatory effects on target tissues and cells; bronchostriction, fever, pain, increased production of inflammatory cytokines such as TNF-alpha and IL-6, platelet aggregation, vasoconstriction, vascular permeability, chemotaxis of leukocytes, and release of reactive oxygen species by granulocytes. Omega-6 fatty acids activate PPAR to the less extent than omega-3 fatty acids, but a study involving human keratinocytes showed induction of COX-2 expression resulting from PPAR-alpha activation. Omega-6 fatty acids are also reported to directly activate syntaxin-3, a plasma protein membrane that regulates vesicle transport and growth of neurites.