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Am J Physiol Endocrinol Metab 287: E120-E127, 2004. First published January 28, 2004; doi:10.1152/ajpendo.00542.2003
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Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle

Matthew J. Watt,1 Anna G. Holmes,1 Gregory R. Steinberg,2 Jose L. Mesa,1 Bruce E. Kemp,2 and Mark A. Febbraio1

1Skeletal Muscle Research Laboratory, Royal Melbourne Institute of Technology, Bundoora, Victoria 3083; and 2St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia

Submitted 30 November 2003 ; accepted in final form 26 January 2004

Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O2 uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased (P < 0.05) plasma FFA at rest and completely suppressed the exercise-induced increase in plasma FFA (180 min: CON, 1.42 ± 0.07; NA, 0.10 ± 0.01 mM). The decreased plasma FFA during NA was associated with decreased (P < 0.05) adipose tissue hormone-sensitive lipase (HSL) activity (CON: 13.9 ± 2.5, NA: 9.1 ± 3.0 nmol·min–1·mg protein–1). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 ± 0.8; NA, 6.3 ± 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 ± 0.07; 180 min: 0.17 ± 0.04 nmol·min–1·mg protein–1). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK){alpha}1 activity was not affected by exercise or NA, whereas AMPK{alpha}2 activity was increased (P < 0.05) from rest during exercise in NA and was greater (P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.

free fatty acids; intramuscular triacylglycerols; hormone-sensitive lipase; glycerol-3-phosphate acyltransferase; enzymatic regulation; exercise; AMP-activated protein kinase



Address for reprint requests and other correspondence: M. J. Watt, Skeletal Muscle Research Laboratory, School of Medical Sciences, RMIT Univ., PO Box 71, Bundoora 3083, Victoria, Australia (E-mail: matthew.watt{at}rmit.edu.au).




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