| 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
|
