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

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, Rasmus Rabøl, Pernille F Svendsen, Mette Skovbro, Robert Christopher Boushel, Steen B Haugaard, Peter Schjerling, Patrick Schrauwen, Matthijs K C Hesselink, Lisbeth NilasSten Madsbad, Flemming Dela

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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.
Original languageEnglish
JournalMetabolism - Clinical and Experimental
Volume58
Issue number8
Pages (from-to)1145-52
Number of pages8
ISSN0026-0495
DOIs
Publication statusPublished - 2009

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