Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss.

• Abstract: 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.
• Authors: Rasmus Rabøl, Pernille F Svendsen, Mette Skovbro, Robert Boushel, Steen B Haugaard, Peter Schjerling, Patrick Schrauwen, Matthijs K C Hesselink, Lisbeth Nilas, Sten Madsbad, Flemming Dela (Affiliation: Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. rasmus.rabol at yale.edu)
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 58 Issue 8 Pg. 1145-52 (Aug 2009) ISSN: 1532-8600 [Electronic] United States
• PMID: 19454354 (Publication Type: Journal Article)

Chemical References

• Biological Markers
• Blood Glucose
• DNA, Mitochondrial
• Fatty Acids, Nonesterified
• Ion Channels
• Mitochondrial Proteins
• Triglycerides
• mitochondrial uncoupling protein 3
• Insulin
• Glycogen
• Citrate (si)-Synthase

Topics

• Adult
• Biological Markers (metabolism)
• Blood Glucose (metabolism)
• Caloric Restriction
• Cell Respiration
• Citrate (si)-Synthase (metabolism)
• DNA, Mitochondrial (metabolism)
• Fatty Acids, Nonesterified (blood)
• Female
• Glucose Tolerance Test
• Glycogen (metabolism)
• Humans
• Insulin (blood)
• Insulin Resistance
• Ion Channels (metabolism)
• Mitochondria, Muscle (metabolism)
• Mitochondrial Proteins (metabolism)
• Muscle, Skeletal (metabolism, physiopathology)
• Obesity (blood, enzymology, metabolism)
• Triglycerides (metabolism)
• Weight Loss