The effects of endotoxaemia and omega-3 fatty acids on membrane fatty acids and cardiac G-proteins
Dietary manipulation was undertaken with the aim of influencing membrane composition and improving adrenergic dysfunction. The objective was to explore the effects of 5 days of continuous intra-duodenal feeding of diets containing n-3 PUFA on myocyte membrane phospholipids, contractility and G-protein. The control diet was omega-6 (n-6) PUFA from safflower oil. The animals were infused with either saline or endotoxin (1 mg/kg) in the last 24 hours. The diets resulted in incorporation of lipids with alteration in myocyte membrane lipid composition. The relative percentage of n-3 PUFA was increased in the fish oil group (22.61± 1.30, 20.46±1.35 for control and endotoxin) compared to safflower oil group (15.21±1.77, 14.16±0.56 for control and endotoxin). The mean inotropic response to isoprenaline was improved by feeding of n-3 PUFA enriched diets (0.175±0.027 for safflower oil endotoxin group vs 0.264±0.03 for safflower oil control, 0.261±0.064 for fish oil control and 0.275±0.073 for fish oil endotoxin group). The adenylyl cyclase activity on forskolin stimulation was not affected by diet or endotoxin (0.165±0.036, 0.176±0.058 for safflower control and endotoxin, and 0.163±0.036, 0.173±0.017 for fish oil control and endotoxin). The data on forskolin stimulation suggested distal contractile mechanisms were intact and that the defect in βAR signal was occurring at a site proximal to adenylyl cyclase. Sodium fluoride, a direct activator of G-proteins revealed a much greater degree of stimulation in the fish oil endotoxin group compared to the safflower oil endotoxin group (0.013±0.030 for safflower oil endotoxin, 0.053±0.015 for fish oil endotoxin and 0.055±0.022 for safflower oil control, 0.088±0.26 for fish oil control). The mean relative percentage of Gαo subunits was reduced in fish oil endotoxin group compared to safflower oil endotoxin group (16.65±3.01 for fish oil endotoxin, 25.37±1.29 for safflower oil endotoxin and 15.63±0.91 for safflower oil control, 13.06±2.70 for fish oil control). In summary, n-3 PUFA improve βAR transmembrane signal in endotoxaemia by favourably altering G-regulatory proteins possibly through membrane displacement of n-6 fatty acids.