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

被引:61
作者
Rabol, Rasmus [1 ,2 ]
Svendsen, Pernille F. [3 ]
Skovbro, Mette [1 ]
Boushel, Robert [1 ]
Haugaard, Steen B. [4 ]
Schjerling, Peter [1 ,5 ]
Schrauwen, Patrick [6 ,7 ]
Hesselink, Matthijs K. C. [6 ,7 ]
Nilas, Lisbeth [3 ]
Madsbad, Sten [2 ]
Dela, Flemming [1 ]
机构
[1] Univ Copenhagen, Fac Hlth Sci, Dept Biomed Sci, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark
[2] Univ Copenhagen, Hvidovre Univ Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark
[3] Univ Copenhagen, Hvidovre Univ Hosp, Dept Gynecol & Obstet, DK-2650 Hvidovre, Denmark
[4] Univ Copenhagen, Hvidovre Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark
[5] Bispebjerg Hosp, Inst Sports Med, DK-2200 Copenhagen, Denmark
[6] Maastricht Univ, Dept Human Biol, NL-6200 MD Maastricht, Netherlands
[7] Maastricht Univ, Dept Movement Sci, NL-6200 MD Maastricht, Netherlands
来源
METABOLISM-CLINICAL AND EXPERIMENTAL | 2009年 / 58卷 / 08期
关键词
INSULIN-RESISTANCE; THYROID-HORMONES; FATTY-ACIDS; CAPACITY; PHOSPHORYLATION; SENSITIVITY; DYSFUNCTION; MECHANISMS; EXPRESSION; TOLERANCE;
D O I
10.1016/j.metabol.2009.03.014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-caloric-induced weight loss ill 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 rnitochondrial 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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:1145 / 1152
页数:8
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