High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass.
It has been variously hypothesized that the insulin resistance induced in rodents by a high-fat diet is due to increased visceral fat accumulation, to an increase in muscle triglyceride (TG) content, or to an effect of diet composition. In this study we used a number of interventions: fish oil, leptin, caloric restriction, and shorter duration of fat feeding, to try to disassociate an increase in visceral fat from muscle insulin resistance. Substituting fish oil (18% of calories) for corn oil in the high-fat diet partially protected against both the increase in visceral fat and muscle insulin resistance without affecting muscle TG content. Injections of leptin during the last 4 days of a 4-wk period on the high-fat diet partially reversed the increase in visceral fat and the muscle insulin resistance, while completely normalizing muscle TG. Restricting intake of the high-fat diet to 75% of ad libitum completely prevented the increase in visceral fat and muscle insulin resistance. Maximally insulin-stimulated glucose transport was negatively correlated with visceral fat mass (P < 0.001) in both the soleus and epitrochlearis muscles and with muscle TG concentration in the soleus (P < 0.05) but not in the epitrochlearis. Thus we were unable to dissociate the increase in visceral fat from muscle insulin resistance using a variety of approaches. These results support the hypothesis that an increase in visceral fat is associated with development of muscle insulin resistance.
Kim
J Y
JY
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nolte
L A
LA
Hansen
P A
PA
Han
D H
DH
Ferguson
K
K
Thompson
P A
PA
Holloszy
J O
JO
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000494:pharmacology*; D002149:Energy Intake; D005395:Fish Oils / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D014316:Tritium; D014781:Viscera
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D004041:Dietary Fats; D005395:Fish Oils; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D014316:Tritium; D008353:Mannitol; D003847:Deoxyglucose