Lipids and Insulin Sensitivity

Skeletal Muscle Lipid Metabolism and Insulin Sensitivity: Can Dietary Fatty Acid Composition Modulate Muscle Lipid Storage?

Rationale: The investigators hypothesize that a change in dietary fat quality (an increase in unsaturated fatty acids) may modulate fuel partitioning within the type 2 diabetic muscle towards less accumulation of lipid metabolites and an improved insulin sensitivity. Objective: The contribution of dietary vs endogenous fat sources to lipid overflow in the circulation and to skeletal muscle lipid uptake and storage in obese insulin resistant subjects vs obese insulin sensitive controls. The acute effect of meals with various fatty acid composition ((high saturated (SFA) vs polyunsaturated (PUFA) vs monounsaturated (MUFA)) on skeletal muscle lipid uptake and storage, fatty acid mediated gene expression and postprandial insulin sensitivity in obese insulin resistant subjects. Study design: single-blind randomized cross-over trial Study population: obese males (35-70 years) with or without insulin resistance Intervention: 1 test meal 3 test meals with a different fatty acid composition Main study parameters/endpoints: More insight whether dietary fat quality may modulate circulating lipids and skeletal muscle fatty acids handling, and may affect oxidative capacity and lipid storage in parallel to an increased insulin sensitivity.

The acute effect of meals with various fatty acid composition ((high saturated (SFA) vs polyunsaturated (PUFA) vs monounsaturated (MUFA)) on postprandial insulin sensitivity will be measured during the stable isotope test.

Using the stable isotope technique, we can differentiate between the metabolic fate of dietary versus endogenous fatty acids

Acute effect of meals with various fatty acid composition on transcriptional regulation of the fatty acid metabolism in skeletal muscle biopsies

Inclusion Criteria: Obese males aged between 35 and 70 years with insulin resistance. Exclusion Criteria: History of type 2 diabetes. Liver or kidney failure. Diseases in which the live expectation is shorter then 5 years. The use of experimental medication. Diseases/medication use that may have an influence on the glucose tolerance. Not to be able to understand the study information. Users of fatty acid supplements including fish oils etc. Users of high doses of antioxidant vitamins. Athletes. People on a diet of people that are planning to lose weight.

Jans A, Konings E, Goossens GH, Bouwman FG, Moors CC, Boekschoten MV, Afman LA, Muller M, Mariman EC, Blaak EE. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity. Am J Clin Nutr. 2012 Apr;95(4):825-36. doi: 10.3945/ajcn.111.028787. Epub 2012 Feb 15.