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Departments of 1 Medicine and 2 Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and 3 Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Ste-Foy, Quebec, Canada G1K 7P4
The current study was undertaken to
investigate fatty acid metabolism by skeletal muscle to examine
potential mechanisms that could lead to increased muscle triglyceride
in obesity. Sixteen lean and 40 obese research volunteers had leg
balance measurement of glucose and free fatty acid (FFA) uptake
(fractional extraction of [9,10
3H]oleate) and indirect
calorimetry across the leg to determine substrate oxidation during
fasting and insulin-stimulated conditions. Muscle obtained by
percutaneous biopsy had lower carnitine palmitoyl transferase (CPT)
activity and oxidative enzyme activity in obesity (P < 0.05). During fasting
conditions, obese subjects had an elevated leg respiratory quotient
(RQ, 0.83 ± 0.02 vs. 0.90 ± 0.01;
P < 0.01) and reduced fat oxidation
but similar FFA uptake across the leg. During insulin infusions, fat
oxidation by leg tissues was suppressed in lean but not obese subjects;
rates of FFA uptake were similar. Fasting values for leg RQ correlated
with insulin sensitivity (r = 
0.57, P < 0.001). Thirty-two
of the obese subjects were restudied after weight loss (WL, 14.0 ± 0.9 kg); insulin sensitivity and insulin suppression of fat
oxidation improved (P < 0.01), but
fasting leg RQ (0.90 ± 0.02 vs. 0.90 ± 0.02, pre-WL vs.
post-WL) and muscle CPT activity did not change. The findings suggest
that triglyceride accumulation in skeletal muscle in obesity derives
from reduced capacity for fat oxidation and that inflexibility in
regulating fat oxidation, more than fatty acid uptake, is related to
insulin resistance.
arteriovenous balance; indirect calorimetry; fatty acid metabolism
Deceased 27 August 1999.
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