Fig. 5

The effects of omega-3 fatty acids on glucose metabolism in insulin-sensitive tissues depend on energy fuels. When glucose serves as the major energy substrate (Clamp), glucose utilization is only marginally affected. With increased postprandial intake of both carbohydrates and lipids (Fed/postprandial), or when fatty acids (FA) serve as the major fuel (Fasting), β-oxidation is stimulated by EPA + DHA via PPARα-signaling [12], which results in reduced glucose utilization (red dashed lines) by several mechanisms involving the Randle cycle (55). Inhibition of glucose oxidation at the level of pyruvate dehydrogenase (PDH) by acetyl-CoA (a) leads also to rerouting of pyruvate to anaplerosis (muscle) and/or gluconeogenesis (liver); citrate accumulation in the cytosol results in inhibition of glucose uptake (b) and inhibition of glycolysis (c) at the level of hexokinase (HK)