Muscle mitochondrial morphology, body composition, and energy expenditure in sedentary individuals

Kirkwood, S.; Zurlo, F.; Larson, K. A.; Ravussin, Éric

doi:10.1152/ajpendo.1991.260.1.e89

Cited by 14 publications

(11 citation statements)

References 20 publications

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“…Using similar methodology (leg balance), this group confirmed their earlier findings by reporting an elevated leg RQ in obese subjects (26). Utilizing an in vitro muscle preparation, Kirkwood et al (29) reported a statistically significant and negative relationship between maximally stimulated muscle respiration and body fat content.…”

Section: Is There a Decrement In The Ability Of Skeletal Muscle To Oxsupporting

confidence: 71%

“…In addition to reductions in enzyme activities linked with FAO, there are also alterations in mitochondrial morphology with obesity. Kirwood et al (29) demonstrated that the central distribution of body fat was associated with a lower mitochondrial density, as determined by electron microscopy. Other work using electron microscopy (27) indicated that skeletal muscle mitochondria were smaller by ~35% in type 2 diabetic and obese subjects compared with lean subjects.…”

Section: Is There a Decrement In The Ability Of Skeletal Muscle To Oxmentioning

confidence: 99%

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Intramuscular lipid oxidation and obesity

Houmard

2008

American Journal of Physiology-Regulatory, Integrative and Comp

102

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There is an accumulating amount of evidence indicating that lipid oxidation is depressed in the skeletal muscle of obese individuals. Decrements in fatty acid oxidation (FAO) have been reported with obesity in models ranging from whole body measurements to isolated skeletal muscle preparations as well as in myotubes raised in culture. This reduction appears to be associated with a depression in the activities of enzymes involved in various steps of lipid oxidation, which subsequently partitions lipid entering the cell toward storage. The defect in FAO in skeletal muscle may be critical in relation to health, as a reduction in the capacity for lipid oxidation could directly or indirectly contribute to the insulin resistance commonly evident with obesity. Although less characterized, a decrement in FAO has also been linked with weight gain, which suggests that this characteristic may be an integral aspect leading to the obese state. In terms of intervention, weight loss does not seem to correct the defect in FAO with obesity. This review will provide evidence supporting a reduction in muscle FAO with obesity.

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Section: Is There a Decrement In The Ability Of Skeletal Muscle To Oxsupporting

confidence: 71%

Section: Is There a Decrement In The Ability Of Skeletal Muscle To Oxmentioning

confidence: 99%

Intramuscular lipid oxidation and obesity

Houmard

2008

American Journal of Physiology-Regulatory, Integrative and Comp

102

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“…In resting muscle, mitochondrial oxidative flux is extremely low (32), with very low [ADP] f and robust (highly negative) Δ G ATP (31). Contractile activity can elicit extremely high oxidative flux, revealing a cellular aerobic scope spanning two orders of magnitude (30).…”

Section: Discussionmentioning

confidence: 99%

Increased Reactive Oxygen Species Production and Lower Abundance of Complex I Subunits and Carnitine Palmitoyltransferase 1B Protein Despite Normal Mitochondrial Respiration in Insulin-Resistant Human Skeletal Muscle

et al. 2010

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OBJECTIVEThe contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle.RESEARCH DESIGN AND METHODSMitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method.RESULTSNADH- and FADH2-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-dl-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B).CONCLUSIONSWe provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.

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“…Importantly, we found substantial interindividual differences in the magnitude of glucose suppression of FOx in vitro. This indicates that factors other than hyperglycemia, such as basal glucose uptake (53,54) and mitochondrial number and function (3,55,56), might play an important role in the regulation of insulin-independent substrate utilization in muscle cells. However, the mechanisms by which glucose elicits a differential effect on FOx in vitro will require further study.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor

Ukropcová

McNeil²,

Sereda³

et al. 2005

J. Clin. Invest.

178

184

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Metabolic flexibility of skeletal muscle, that is, the preference for fat oxidation (FOx) during fasting and for carbohydrate oxidation in response to insulin, is decreased during insulin resistance. The aim of this study was to test the hypothesis that the capacity of myotubes to oxidize fat in vitro reflects the donor's metabolic characteristics. Insulin sensitivity (IS) and metabolic flexibility of 16 healthy, young male subjects was determined by euglycemic hyperinsulinemic clamp. Muscle samples were obtained from vastus lateralis, cultured, and differentiated into myotubes. In human myotubes in vitro, we measured suppressibility (glucose suppression of FOx) and adaptability (an increase in FOx in the presence of high palmitate concentration). We termed these dynamic changes in FOx metabolic switching. In vivo, metabolic flexibility was positively correlated with IS and maximal oxygen uptake and inversely correlated with percent body fat. In vitro suppressibility was inversely correlated with IS and metabolic flexibility and positively correlated with body fat and fasting FFA levels. Adaptability was negatively associated with percent body fat and fasting insulin and positively correlated with IS and metabolic flexibility. The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment, which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle. IntroductionObesity and type 2 diabetes are characterized by an increase in body fat, a decrease in insulin-stimulated glucose disposal, and disturbances of oxidative metabolism. Skeletal muscle, the organ responsible for the majority of insulin-stimulated glucose uptake, has a decreased oxidative capacity in obesity and diabetes (1-3) and after weight loss (4-7). Furthermore, Zurlo (8) and others (9-11) showed that decreased fat oxidation (FOx) (represented by a higher respiratory quotient [RQ], the ratio of CO 2 produced to O 2 consumed) is a predictor of weight gain, which suggests the importance of early defects in FOx for future development of obesity and diabetes. Defects in skeletal muscle oxidative capacity and fat metabolism are highly correlated with insulin sensitivity (IS) (1,5,12) and are believed to contribute to the pathogenesis of insulin resistance (13,14).A high-fat diet (HFD) challenges the oxidative machinery of skeletal muscle. Substantial variability exists in the ability of individuals to adapt to HFD by increasing FOx (15). An imbalance between fat intake and FOx results in a positive fat balance (15). Decreased adaptation to HFD has been observed in restrained eaters (16), formerly obese (17, 18) and obese individuals (19), and individuals with a family history of obesity (20). The latter study points toward a possible genetic basis for reduced FOx. Attenuated adaptation to HFD might represent yet another feature of "metabolic inflexibility," the impaired ability of skeletal muscle to switch from carbohydrate to fat oxidation during...

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Muscle mitochondrial morphology, body composition, and energy expenditure in sedentary individuals

Cited by 14 publications

References 20 publications

Intramuscular lipid oxidation and obesity

Intramuscular lipid oxidation and obesity

Increased Reactive Oxygen Species Production and Lower Abundance of Complex I Subunits and Carnitine Palmitoyltransferase 1B Protein Despite Normal Mitochondrial Respiration in Insulin-Resistant Human Skeletal Muscle

Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor

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