High oxidative capacity due to chronic exercise training attenuates lipid-induced insulin resistance.
Fat accumulation in skeletal muscle combined with low mitochondrial oxidative capacity is associated with insulin resistance (IR). Endurance-trained athletes, characterized by a high oxidative capacity, have elevated intramyocellular lipids, yet are highly insulin sensitive. We tested the hypothesis that a high oxidative capacity could attenuate lipid-induced IR. Nine endurance-trained (age = 23.4 ± 0.9 years; BMI = 21.2 ± 0.6 kg/m(2)) and 10 untrained subjects (age = 21.9 ± 0.9 years; BMI = 22.8 ± 0.6 kg/m(2)) were included and underwent a clamp with either infusion of glycerol or intralipid. Muscle biopsies were taken to perform high-resolution respirometry and protein phosphorylation/expression. Trained subjects had ~32% higher mitochondrial capacity and ~22% higher insulin sensitivity (P < 0.05 for both). Lipid infusion reduced insulin-stimulated glucose uptake by 63% in untrained subjects (P < 0.05), whereas this effect was blunted in trained subjects (29%, P < 0.05). In untrained subjects, lipid infusion reduced oxidative and nonoxidative glucose disposal (NOGD), whereas trained subjects were completely protected against lipid-induced reduction in NOGD, supported by dephosphorylation of glycogen synthase. We conclude that chronic exercise training attenuates lipid-induced IR and specifically attenuates the lipid-induced reduction in NOGD. Signaling data support the notion that high glucose uptake in trained subjects is maintained by shuttling glucose toward storage as glycogen.
Department of Human Biology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Esther
E
Phielix
Ruth
R
Meex
D Margriet
DM
Ouwens
Lauren
L
Sparks
Joris
J
Hoeks
Gert
G
Schaart
Esther
E
Moonen-Kornips
Matthijs K C
MK
Hesselink
Patrick
P
Schrauwen
D004655:Emulsions / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000494:pharmacology; D010766:Phosphorylation; D010807:Physical Endurance / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013024:Soybean Oil / Q000494:pharmacology; D055815:Young Adult
D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D007328:Insulin; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil