Uptake of dihomo-gamma-linolenic acid by murine macrophages increases series-1 prostaglandin release following lipopolysaccharide treatment.

Administration of dihomo-gamma-linolenic acid is useful for atopic dermatitis and atherosclerosis in mice; however, the metabolites of dihomo-gamma-linolenic acid have been little studied. We employed a method which enabled simultaneous analysis of nine prostaglandins using liquid chromatography-tandem mass spectrometry, and determined the concentrations of prostaglandins in the supernatants of cultures of mouse peritoneal macrophages stimulated with lipopolysaccharide after pre-incubation with dihomo-gamma-linolenic acid, arachidonic acid, or eicosapentaenoic acid. Accumulated prostaglandin concentrations from mouse macrophages with dihomo-gamma-linolenic acid uptake increased in a dihomo-gamma-linolenic acid concentration-dependent fashion. These increases were mainly due to prostaglandin D(1) and prostaglandin E(1). The order of accumulated prostaglandin concentrations was dihomo-gamma-linolenic acid>arachidonic acid>eicosapentaenoic acid in supernatants with the same concentration of polyunsaturated fatty acid. Since mouse macrophages can clearly produce series-1 prostaglandins, they must be formed in vivo. These findings suggest that the effects of dihomo-gamma-linolenic acid on diseases may be due to series-1 prostaglandins.

Anti-atherosclerotic effects of dihomo-gamma-linolenic acid in ApoE-deficient mice.

AIM: Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid that is mainly metabolized to an anti-inflammatory eicosanoid, prostaglandin (PG) E1, via the cyclooxygenase (COX) pathway. We evaluated the effect of DGLA on atherosclerosis in apoE-deficient mice and studied the mechanism of the anti-atherosclerotic effect. METHODS: ApoE-deficient mice were fed a normal diet supplemented with 0.5% DGLA or vehicle for 6 months. ApoE-deficient mice were also fed a high-cholesterol diet supplemented with 0.5% DGLA or vehicle for 1 month. To clarify the influence of a COX inhibitor, naproxen, on the anti-atherosclerotic effect of DGLA, age-matched apoE-deficient mice fed a high-cholesterol diet supplemented with 0.5% DGLA were given oral naproxen for 1 month. RESULTS: In normal diet-fed mice, acetylcholine-induced vascular relaxation was significantly greater in the DGLA group than in the vehicle group. NADPH oxidase subunits, p22phox and gp91phox, intercellular adhesion molecule-1, and vascular cellular adhesion molecule-1 were significantly lower in the DGLA group than in the vehicle group, and DGLA significantly prevented atherosclerosis. In high-cholesterol diet-fed mice, DGLA also significantly prevented atherosclerosis, but the anti-atherosclerotic effect was attenuated by naproxen. CONCLUSION: DGLA may have an anti-atherosclerotic effect in apoE-deficient mice via PGE1 formation.

Oral supplementation with dihomo-gamma-linolenic acid-enriched oil altered serum fatty acids in healthy men.

Dihomo-gamma-linolenic acid (DGLA)-enriched oil (50 or 150 mg as free DGLA) was administered to healthy men for 4 weeks. The DGLA content in serum phospholipids dose-dependently increased and returned to the initial level after a 4-week washout. No side effects or changes in platelet aggregation were observed. These results indicate that oral supplementation with DGLA oil can safely increase serum DGLA content.