Effect of N3-polyunsaturated fatty acids on peripheral insulin sensitivity.

Fatty acids (FA) are no longer considered solely as a source of energy but also as potent regulators of intermediary metabolism. N3-poly unsaturated fatty acids (N3-PUFA) have been shown to be associated with a lower prevalence of cardiovascular diseases. FA are also involved in obesity induced insulin resistance and DM2. Saturated fatty acids are known for their negative interference on insulin stimulated glucose uptake in peripheral tissues. We recently studied the effect of two different intravenous lipid emulsions containing a mixture of MUFA, PUFA and saturated fatty acids on insulin sensitivity (MEC 05-295) and found insulin resistance but no difference between the two different lipid emulsions. Lipid emulsions for parenteral nutrition containing fish oil are now available. SMOFlipid emulsion is commercially available and based on 30% soy-bean oil, 30% medium chain triglycerides (MCT), 25% olive oil and 15% fish oil. We hypothesize that SMOFlipid® has a less profound effect on insulin sensitivity compared to the two earlier studied lipid emulsions.

1. SMOFlipid® decreases peripheral insulin sensitivity to a lesser extent compared to the other lipid emulsions, Intralipid® and Clinoleic®, due to the lower n6/n3 ratio and the higher MCT concentration in the SMOFlipid emulsion;

2. SMOFlipid®, rich in specific N3-PUFA and MCT, affects not only the serum fatty acid composition but also the concentrations of bioactive lipids within skeletal muscle.

Every participant will serve as his own control and study days will be performed in random assignment. Both study days for one individual will be scheduled at least two weeks apart.

Hyperinsulinemic euglycemic clamp with stable isotopes and concomitant infusion of a fish oil containing lipid emulsion, SMOFlipid®, on one occasion, and control saline infusion on the other occasion. Infusion will take 6 hours. FFA levels will be clamped at approximately 0.5 mmol/L. At the end of both clamps a muscle biopsy from the musculus vastus lateralis will be performed. Each participant will serve as its own control. Studies will be performed in balanced assignment.