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

Rabøl, Rasmus; Svendsen, Pernille Fog; Skovbro, Mette; Boushel, Robert; Haugaard, Steen B.; Schjerling, Peter; Schrauwen, Patrick; Hesselink, Matthijs K. C.; Nilas, Lisbeth; Madsbad, Sten; Dela, Flemming

doi:10.1016/j.metabol.2009.03.014

Cited by 68 publications

(57 citation statements)

References 41 publications

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“…As in several of our previous studies, we did not find any significant correlation between mitochondrial function and measures of insulin sensitivity (12)(13)(14)(15)(16) challenging the concept of a direct causal relationship between mitochondrial function and IR.…”

Section: Discussionsupporting

confidence: 75%

“…Muscle biopsies were taken at baseline before the clamp was performed. A small part of the biopsy sample (5 mg) was immediately placed in ice-cold relaxing (BIOPS) solution and treated with saponin (50 mg/ml) as described previously (12). Measurements of oxygen consumption were performed at 37 8C using a high-resolution respirometer (Oroboros Instruments, Innsbruck, Austria), see below.…”

Section: Muscle Biopsiesmentioning

confidence: 99%

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Skeletal muscle mitochondrial function in polycystic ovarian syndrome

Rabøl

Svendsen²,

Skovbro

et al. 2011

European Journal of Endocrinology

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Objective: Polycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance (IR), which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry. Methods: Hyperinsulinemic-euglycemic clamps (40 mU/min per m 2 ) and muscle biopsies were performed on 23 women with PCOS (nine lean (body mass index (BMI) !25 kg/m 2 ) and 14 obese (BMI O25 kg/m 2 )) and 17 age-and weight-matched controls (six lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function. Results: Insulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex ICII were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mitochondrial DNA/genomic DNA. We found no correlation between mitochondrial function and indices of insulin sensitivity. Conclusions: In contrast to previous reports, we found no evidence that skeletal muscle mitochondrial respiration is reduced in skeletal muscle of women with PCOS compared with control subjects. Furthermore, mitochondrial content did not differ between our control and PCOS groups. These results question the causal relationship between reduced mitochondrial function and skeletal muscle IR in PCOS.

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Section: Discussionsupporting

confidence: 75%

Section: Muscle Biopsiesmentioning

confidence: 99%

Skeletal muscle mitochondrial function in polycystic ovarian syndrome

Rabøl

Svendsen²,

Skovbro

et al. 2011

European Journal of Endocrinology

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“…13 In this study, we also found no reduction in mitochondrial respiration in O individuals, supporting the concept that mitochondrial function is not impaired in obesity. Acute weight loss seems to reduce skeletal muscle mitochondrial respiration, 57 but very few data are available in relation to weight loss and mitochondrial respiration in humans. In our study, PO individuals had similar mitochondrial respiration after long-term weight loss as Cs.…”

Section: Discussionmentioning

confidence: 99%

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans

et al. 2010

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Aim/hypothesis: The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age-and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss. Methods: Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O 2 flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry. Results: During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C. Conclusions: In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.

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“…The inflexible state of metabolism results from a discordant attempt of numerous peripheral tissues to respond to changing fuel needs and nutrient availability, yielding little or no discernable response. Metabolic inflexibility is a common characteristic of obesity (119,220), and energy-restricted weight loss reverses many of its associated impairments in metabolic regulation (48,81,158,188,219). Because enhanced metabolic flexibility improves the metabolic response to ingested energy, it alters the peripheral signals of nutrient status that are sent to the brain during weight maintenance and during weight regain (Fig.…”

Section: Enhanced Metabolic Flexibility: Improved Nutrient Clearancementioning

confidence: 99%

“…Unlike lean subjects, energy-restricted weight loss in obese subjects fails to increase skeletal muscle oxidative capacity (215,225,226) unless the energy-restricted diet is accompanied by regular exercise (96,207,208). Mitochondrial respiratory capacity declines (188), glycolytic capacity declines (87,215), and the expression of enzymes associated with ␤-oxidation and mitochondrial enzyme activities remain low and, if anything, decline (62,188,215,225). Collectively, these adaptations in muscle underlie the reduced energy requirements, the increased metabolic efficiency, and the enhanced muscle work efficiency observed with energyrestricted weight loss in postobese subjects (192,198) (Fig.…”

Section: Skeletal Muscle: Reduced Energy Requirements and A Preferencmentioning

confidence: 99%

Biology's response to dieting: the impetus for weight regain

MacLean

Bergouignan

Cornier

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

374

326

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Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the "energy depletion" signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter. energy restriction; diet-induced obesity; obesity prone; weight loss; energy balance IN THE UNITED STATES, OVER 60% of adults and close to 20% of children are overweight or obese (35,174). A number of effective weight loss strategies are available, but most are only transiently effective over a period of 3 to 6 mo. Less than 20% of individuals that have attempted to lose weight are able to achieve and maintain a 10% reduction over a year (128). Over one-third of lost weight tends to return within the first year, and the majority is gained back within 3 to 5 years (3,246). A number of reasons have been proposed for the high incidence of weight regain (69,246), and several point to the biological response to weight loss.The objective of this review is to examine the role of this biological response in the process of weight regain. Biological regulation is first discussed in relation to other nonbiological pressures that affect body weight as weight is gained, lost, and regained. The specific biological adaptations to the most common form of dieting, an energy-restricted low-fat diet, are then discussed in more detail. Previous reviews provide extensive descriptions of the normal adaptive response to energy restriction. We do not attempt to recapitulate those efforts here. Rather, the unique perspective of this review summarizes those adaptations that have been confirmed o...

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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

Cited by 68 publications

References 41 publications

Skeletal muscle mitochondrial function in polycystic ovarian syndrome

Skeletal muscle mitochondrial function in polycystic ovarian syndrome

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans

Biology's response to dieting: the impetus for weight regain

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