title: 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.affiliation: Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. rasmus.rabol@yale.edu
authors.forename: Rasmus
authors.initials: R
authors.lastname: Rabøl
authors.forename: Pernille F
authors.initials: PF
authors.lastname: Svendsen
authors.forename: Mette
authors.initials: M
authors.lastname: Skovbro
authors.forename: Robert
authors.initials: R
authors.lastname: Boushel
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Nilas
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D019069:Cell Respiration; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007473:Ion Channels / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D000071247:Uncoupling Protein 3; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004272:DNA, Mitochondrial; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D014280:Triglycerides; D000071247:Uncoupling Protein 3; D006003:Glycogen; D002950:Citrate (si)-Synthase