Chronological approach of diet-induced alterations in muscle mitochondrial functions in rats.
OBJECTIVE
Mitochondrial dysfunction might predispose individuals to develop insulin resistance. Our objective was to determine whether mitochondrial dysfunction or insulin resistance was the primary event during high-fat (HF) diet.


METHODS
Rats were fed an HF diet for 0, 3, 6, 9, 14, 20, or 40 days and compared with control. Soleus and tibialis muscle mitochondrial activity were assessed using permeabilized fiber technique. Insulin [area under the curve for insulin (AUC(I))] and glucose [area under the curve for glucose (AUC(G))] responses to intraperitoneal glucose tolerance test as well as fasting plasma non-esterified fatty acids (NEFAs), triglyceride, and glycerol concentrations were determined.


RESULTS
AUC(I) and AUC(G) were altered from Day 6 (p < 0.01 vs. Day 0). In soleus, oxidative phosphorylation (OXPHOS) activity was transiently enhanced by 26% after 14 days of HF diet (p < 0.05 vs. Day 0) conjointly with 62% increase in NEFA concentration (p < 0.05 vs. Day 0). This was associated with normalized AUC(G) at Day 14 and with a decline of plasma NEFA concentration together with stabilization of intra-abdominal adiposity at Day 20. Prolongation of HF diet again caused an increase in plasma NEFA concentration, intra-abdominal adiposity, AUC(I), and AUC(G). At Day 40, significant decrease in OXPHOS activity was observed in soleus.


CONCLUSIONS
Mitochondria first adapt to overfeeding in oxidative muscle limiting excess fat deposition. This potentially contributes to maintain glucose homeostasis. Persistent overfeeding causes insulin resistance and results in a slow decline in oxidative muscle OXPHOS activity. This shows that the involvement of mitochondria in the predisposition to insulin resistance is mainly due to an inability to face prolonged excess fat delivery.
Chanséaume
Emilie
E
Lipid and Energy Metabolism Research Unit, Human Nutrition Laboratory, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1019, Clermont-Ferrand, France.
Tardy
Anne-Laure
AL
Salles
Jérôme
J
Giraudet
Christophe
C
Rousset
Paulette
P
Tissandier
Antoine
A
Boirie
Yves
Y
Morio
Béatrice
B
D000222:Adaptation, Physiological; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D005990:Glycerol