Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men.
OBJECTIVE
A high-fructose diet (HFrD) may play a role in the obesity and metabolic disorders epidemic. In rodents, HFrD leads to insulin resistance and ectopic lipid deposition. In healthy humans, a four-week HFrD alters lipid homoeostasis, but does not affect insulin sensitivity or intramyocellular lipids (IMCL). The aim of this study was to investigate whether fructose may induce early molecular changes in skeletal muscle prior to the development of whole-body insulin resistance.


METHODS
Muscle biopsies were taken from five healthy men who had participated in a previous four-week HFrD study, during which insulin sensitivity (hyperinsulinaemic euglycaemic clamp), and intrahepatocellular lipids and IMCL were assessed before and after HFrD. The mRNA concentrations of 16 genes involved in lipid and carbohydrate metabolism were quantified before and after HFrD by real-time quantitative PCR.


RESULTS
HFrD significantly (P<0.05) increased stearoyl-CoA desaturase-1 (SCD-1) (+50%). Glucose transporter-4 (GLUT-4) decreased by 27% and acetyl-CoA carboxylase-2 decreased by 48%. A trend toward decreased peroxisomal proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was observed (-26%, P=0.06). All other genes showed no significant changes.


CONCLUSIONS
HFrD led to alterations of SCD-1, GLUT-4 and PGC-1alpha, which may be early markers of insulin resistance.
Department of Physiology, University of Lausanne, 7, rue du Bugnon, 1005 Lausanne, Switzerland.
K-A
KA
Lê
D
D
Faeh
R
R
Stettler
C
C
Debard
E
E
Loizon
H
H
Vidal
C
C
Boesch
E
E
Ravussin
L
L
Tappy
D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D044465:White People
D004040:Dietary Carbohydrates; D005632:Fructose