retracted

0 downloads 0 Views 3MB Size Report
markedly for cardiovascular and metabolic disease risk factors. ... Animals (generation 16) differed for endurance running capacity by 295%. LCR ... In order to approach progressive metabolic disease states mechanistically, we recently ... of lipid metabolism in aerobic exercise capacity we hypothesized that the low intrinsic.
Page 1 of 29

DYSREGULATION OF MUSCLE LIPID METABOLISM IN RATS SELECTIVELY BRED FOR LOW AEROBIC RUNNING CAPACITY

Running Head: Lipid metabolism and exercise capacity Fiona J. Spargo1, Sean L. McGee2, Nick Dzamko3, Matthew J. Watt3, Bruce E. Kemp3, Steven L. Britton4, Lauren G. Koch4, Mark Hargreaves2, John A. Hawley1

1

Exercise Metabolism Laboratory, RMIT University, Victoria, Australia

2

Department of Physiology, University of Melbourne, Victoria, Australia

3

4

D ec TR em A be CT r E 20 D 07

St Vincent’s Institute of Medical Research and the Department of Medicine, Fitzroy, Victoria, Australia Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan, US

Address correspondence to: John A. Hawley, Ph.D. Exercise Metabolism Group School of Medical Sciences

PO Box 71

Bundoora

R

Plenty Road

E

RMIT University

Victoria 3083 Australia

Ph: + 61 3 9925 7353 Fax: +61 3 9467 8181 Email: [email protected]

Page 2 of 29

2 ABSTRACT 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- (LCR) and high-capacity runners (HCR) that also differ 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 had higher resting plasma glucose (6.58 ±0.45 vs. 6.09 ±0.45 mmol/L), insulin (0.48 ±0.03

D ec TR em A be CT r E 20 D 07

vs. 0.32 ±0.02 ng/mL), non-esterified fatty acid (NEFA; 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