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1 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1; and 2 Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
The
adipocyte-derived hormone leptin has been shown to acutely increase
fatty acid (FA) oxidation and decrease esterification in resting rodent
skeletal muscle. However, the effects of leptin on human skeletal
muscle FA metabolism are completely unknown. In these studies, we have
utilized an isolated human skeletal muscle preparation combined with
the pulse-chase technique to measure FA metabolism with and without
leptin in lean and obese human skeletal muscle. Under basal conditions
(in the absence of leptin), muscle from the obese demonstrated
significantly elevated levels of total FA uptake (+72%,
P = 0.038) and enhanced rates of FA esterification into
triacylglycerol (+102%, P = 0.042) compared with lean
subjects. In the presence of leptin, lean muscle had elevated rates of
endogenous (+103%, P = 0.01) and exogenous (+150%, P = 0.03) palmitate oxidation. When the ratio of
esterification to exogenous oxidation was examined, leptin reduced this
ratio (
47%, P = 0.032), demonstrating the increased
partitioning of FA toward oxidation and away from storage. Contrary to
these findings in lean muscle, leptin had no effect on FA metabolism in
skeletal muscle of the obese. This study provides the first evidence
that leptin increases FA oxidation in skeletal muscle of lean, but not
obese humans, thus demonstrating the development of leptin resistance
in obese human skeletal muscle.
pulse-chase technique; triacylglycerol; rectus abdominus
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