Lifestyle changes and lipid metabolism gene expression and protein content in skeletal muscle of subjects with impaired glucose tolerance.

Aims/hypothesis: Skeletal muscle of pre-diabetic patients is characterised by a diminished capacity to handle fatty acids. A diminished content of several enzymes involved in fatty-acid transport and oxidation have been suggested to underlie these defects. The aim of this study was to investigate whether the combination of dietary advice, increased physical activity and weight loss improves lipid metabolic gene and protein expression in skeletal muscle of subjects with impaired glucose tolerance.

Methods: Before and after 1 year of a lifestyle-intervention programme, expression of several genes and proteins involved in lipid metabolism were measured in vastus lateralis muscle biopsies from subjects in the intervention ( n=7) and control group ( n=6).

Results: After 1 year the intervention group had an improved glycaemic control and reduced body fat compared to the control group. Significant differences were observed for acetyl CoA-carboxylase 2 and uncoupling protein 2 expression (ACC2: -16.8+/-12.4% vs +51.5+/-32.3% for the intervention and control group respectively; p<0.05) (UCP2: -26.9+/-10.3% vs +10.5+/-6.2% for the intervention and control group respectively; p<0.05). Change in 3-hydroxyacyl-CoA dehydrogenase protein content tended to be different between groups (+3.2+/-1.1 vs -0.9+/-1.9 U/mg.ww for the intervention and control group, p=0.07).

Conclusions/interpretation: Lifestyle changes leading to an improved glycaemic control and reduced adiposity, resulted in a down-regulation of ACC-2 and UCP2 expression and in an increase in HAD protein content, reflecting a better capacity to utilise fatty acids.