Dysregulation of muscle lipid metabolism in rats selectively bred for low aerobic running capacity.
As substrate for evaluation of metabolic diseases, we developed novel rat models that contrast for endurance exercise capacity. Through two-way artificial selection, we created rodent phenotypes of intrinsically low-capacity runners (LCR) and high-capacity runners (HCR) that also differed markedly for cardiovascular and metabolic disease risk factors. Here, we determined skeletal muscle proteins with putative roles in lipid and carbohydrate metabolism to better understand the mechanisms underlying differences in whole body substrate handling between phenotypes. Animals (generation 16) differed for endurance running capacity by 295%. LCR animals had higher resting plasma glucose (6.58 +/- 0.45 vs. 6.09 +/- 0.45 mmol/l), insulin (0.48 +/- 0.03 vs. 0.32 +/- 0.02 ng/ml), nonesterified fatty acid (0.57 +/- 0.14 v 0.35 +/- 0.05 mM), and triglyceride (TG; 0.47 +/- 0.11 vs. 0.25 +/- 0.08 mmol/l) concentrations (all P < 0.05). Muscle TG (72.3 +/- 14.7 vs. 38.9 +/- 6.2 mmol/kg dry muscle wt; P < 0.05) and diacylglycerol (96 +/- 28 vs. 42 +/- 8 pmol/mg dry muscle wt; P < 0.05) contents were elevated in LCR vs. HCR rats. Accompanying the greater lipid accretion in LCR was increased fatty acid translocase/CD36 content (1,014 +/- 80 vs. 781 +/- 70 arbitrary units; P < 0.05) and reduced TG lipase activity (0.158 +/- 0.0125 vs. 0.274 +/- 0.018 mmol.min(-1).kg dry muscle wt(-1); P < 0.05). Muscle glycogen, GLUT4 protein, and basal phosphorylation states of AMP-activated protein kinase-alpha1, AMP-activated protein kinase-alpha2, and acetyl-CoA carboxylase were similar in LCR and HCR. In conclusion, rats with low intrinsic aerobic capacity demonstrate abnormalities in lipid-handling capacity. These disruptions may, in part, be responsible for the increased risk of metabolic disorders observed in this phenotype.
Spargo
Fiona J
FJ
Exercise Metabolism Group, School of Medical Sciences, Australia.
McGee
Sean L
SL
Dzamko
Nick
N
Watt
Matthew J
MJ
Kemp
Bruce E
BE
Britton
Steven L
SL
Koch
Lauren G
LG
Hargreaves
Mark
M
Hawley
John A
JA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism*; D009929:Organ Size; D010807:Physical Endurance / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012420:Running / Q000502:physiology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009124:Muscle Proteins; D014280:Triglycerides; D008049:Lipase