PhD Louise D Høeg – University of Copenhagen

PhD Louise D Høeg

Department of Nutrition, Exercise and Sports

Affiliated with UNIK project no. 15

Title of thesis: Regulation of skeletal muscle insulin action in relation to dietary fatty acids and gender

Thesis summary: In the present thesis the aims were 1) to investigate whether insulin sensitivity was different between women and men and whether a lipid load induced insulin resistance to a similar extent in women and men, 2) to determine whether lipid-induced insulin resistance was due to energy surplus or dietary fatty acid quality and/or chain-length, 3) to investigate molecular mechanisms underlying lipid-induced insulin resistance.

Results from studies provided in this thesis showed that insulin stimulated glucose uptake in skeletal muscle was higher in women than in matched men. When increasing fatty acid availability by intralipid infusion, whole-body insulin sensitivity was reduced by 38% in men, whereas the reduction was significantly less in women (26%) compared with the control situation, suggesting that women are less prone to develop acute lipid-induced insulin resistance on a whole-body level compared with men. After consuming a hypercaloric fat-rich diet (80 E%) enriched in unsaturated fatty acids for three days, reduced insulin stimulated whole-body (20%) and skeletal muscle glucose uptake (28%) were observed in men compared with a isocaloric control diet. After consuming a fat-rich diet enriched in long-chain saturated fatty acids, whole body insulin sensitivity (19%) and insulin stimulated glucose uptake in skeletal muscle (24%) were also reduced, whereas no changes was observed after a diet enriched in medium-chain saturated fatty acids and carbohydrates. These findings show that insulin sensitivity was influenced by quality and chain-length of fatty acids rather than energy surplus per se.

The lipid-induced reduction in skeletal muscle insulin sensitivity was observed without changes in the proximal insulin signaling cascade. The lipid-induced decrease in insulin sensitivity in skeletal muscle could rather be ascribed to attenuated GLUT4 translocation to the plasma surface membrane after the unsaturated (23%) and long-chain saturated fatty acid diet (26%) compared with the control diet (52%)(investigated in rats). Furthermore, the present data suggest that mechanisms regulating GLUT4 translocation and insulin stimulated glucose uptake in skeletal muscle were dietary fatty acid specific depended. 


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