Reduced oxidative capacity of skeletal muscle has been proposed to lead to accumulation
of intramyocellular triglyceride (IMTG) and insulin resistance. We have measured mitochondrial
respiration before and after a 10% low-calorie-induced weight loss in young obese
women to examine the relationship between mitochondrial function, IMTG, and insulin
resistance. Nine obese women (age, 32.3 years [SD, 3.0]; body mass index, 33.4 kg/m(2)
[SD, 2.6]) completed a 53-day (SE, 3.8) very low calorie diet (VLCD) of 500 to 600
kcal/d without altering physical activity. The target of the intervention was a 10%
weight loss; and measurements of mitochondrial respiration, IMTG, respiratory exchange
ratio, citrate synthase activity, mitochondrial DNA copy number, plasma insulin, 2-hour
oral glucose tolerance test, and free fatty acids were performed before and after
weight loss. Mitochondrial respiration was measured in permeabilized muscle fibers
using high-resolution respirometry. Average weight loss was 11.5% (P < .05), but the
levels of IMTG remained unchanged. Fasting plasma glucose, plasma insulin homeostasis
model assessment of insulin resistance, and insulin sensitivity index (composite)
obtained during 2-hour oral glucose tolerance test improved significantly. Mitochondrial
respiration per milligram tissue decreased by approximately 25% (P < .05), but citrate
synthase activity and mitochondrial DNA copy number remained unchanged. Respiratory
exchange ratio decreased from 0.87 (SE, 0.01) to 0.79 (SE, 0.02) (P < .05) as a sign
of increased whole-body fat oxidation. Markers of insulin sensitivity improved after
the very low calorie diet; but mitochondrial function decreased, and IMTG remained
unchanged. Our results do not support a direct relationship between mitochondrial
function and insulin resistance in young obese women and do not support a direct relationship
between IMTG and insulin sensitivity in young obese women during weight loss.