Expression of genes involved in lipid metabolism in men with impaired glucose tolerance: impact of insulin stimulation and weight loss.
BACKGROUND
The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of weight loss.


METHODS
Seven IGT men and 5 men with normal glucose tolerance (NGT), comparable in terms of age and BMI, participated in the study. The 5 IGT men followed a 12-week weight loss program. Muscle biopsies were taken and the expression of 6 genes was investigated.


RESULTS
Subjects had a reduction of 15.5 ± 4.3 kg in body weight. Baseline gene expression was not different between NGT and IGT men. After a hyperinsulinemic clamp, there was an overall upregulation of PGC1α, SREBP-1c, SREBP-2, and ACC-2. The upregulation of SREBP-2 was more pronounced in IGT men (p = 0.049). Weight loss significantly increased insulin sensitivity by 71%, which was not reflected in altered gene expression profiles.


CONCLUSIONS
SREBP-2 shows altered insulin responsiveness in IGT men compared with NGT men, while there were no differences in basal gene expression.
Konings
E
E
Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands. ellen.konings@hb.unimaas.nl
Corpeleijn
E
E
Bouwman
F G
FG
Mariman
E C
EC
Blaak
E E
EE
D015992:Body Mass Index; D017931:DNA Primers; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015431:Weight Loss
D017931:DNA Primers; D005227:Fatty Acids; D012333:RNA, Messenger