Differences in proton leak kinetics, but not in UCP3 protein content, in subsarcolemmal and intermyofibrillar skeletal muscle mitochondria from fed and fasted rats

Iossa, Susanna; Lionetti, Lillà; Mollica, Maria Pina; Crescenzo, Raffaella; Botta, Monica; Samec, Sonia; Dulloo, Abdul G.; Liverini, Giovanna

doi:10.1016/s0014-5793(01)02772-7

Cited by 21 publications

(30 citation statements)

References 35 publications

(45 reference statements)

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“…Our data show that the differential expression of UCP3 contributes further to the unique constitution of each mitochondrial subfraction. In contrast to our findings, Jimenez et al (32) have detailed a higher basal UCP3 expression in the SS subfraction isolated from mouse TA, whereas Iossa et al (28) found no difference in rat skeletal muscle UCP3 content between IMF and SS mitochondria. We cannot explain these discrepant results other than to propose either species (32) or methodological differences (28).…”

Section: Discussioncontrasting

confidence: 99%

“…State 4 mitochondrial respiration rates were 2.6-fold greater in IMF mitochondria than those observed in the SS mitochondrial subfraction (P Ͻ 0.05; Fig. 1A), in agreement with previous studies (10,28,37). In contrast, UCP3 protein levels were only 1.3-fold greater in IMF mitochondria, compared with the SS subfraction (P Ͻ 0.05; Fig.…”

Section: Resultssupporting

confidence: 92%

“…State 4 respiration represents one of a number of functional and biochemical parameters that are distinct between the two mitochondrial subpopulations (3,10,28,37). Our data show that the differential expression of UCP3 contributes further to the unique constitution of each mitochondrial subfraction.…”

Section: Discussionmentioning

confidence: 73%

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Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis

Ljubicic

Adhihetty²,

Hood³

2004

Journal of Applied Physiology

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Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis. J Appl Physiol 97: 976 -983, 2004. First published May 14, 2004 10.1152/japplphysiol.00336.2004In an effort to better characterize uncoupling protein-3 (UCP3) function in skeletal muscle, we assessed basal UCP3 protein content in rat intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial subfractions in conjunction with measurements of state 4 respiration. UCP3 content was 1.3-fold (P Ͻ 0.05) greater in IMF compared with SS mitochondria. State 4 respiration was 2.6-fold greater (P Ͻ 0.05) in the IMF subfraction than in SS mitochondria. GDP attenuated state 4 respiration by ϳ40% (P Ͻ 0.05) in both subfractions. The UCP3 activator oleic acid (OA) significantly increased state 4 respiration in IMF mitochondria only. We used chronic electrical stimulation (3 h/day for 7 days) to investigate the relationship between changes in UCP3 protein expression and alterations in state 4 respiration during contractile activity-induced mitochondrial biogenesis. UCP3 content was increased by 1.9-and 2.3-fold in IMF and SS mitochondria, respectively, which exceeded the concurrent 40% (P Ͻ 0.05) increase in cytochrome-c oxidase activity. Chronic contractile activity increased state 4 respiration by 1.4-fold (P Ͻ 0.05) in IMF mitochondria, but no effect was observed in the SS subfraction. The uncoupling function of UCP3 accounted for 50 -57% of the OA-induced increase in state 4 respiration in IMF mitochondria, which was independent of the induced twofold difference in UCP3 content due to chronic contractile activity. Thus modifications in UCP3 function are more important than changes in UCP3 expression in modifying state 4 respiration. This effect is evident in IMF but not SS mitochondria. We conclude that UCP3 at physiological concentrations accounts for a significant portion of state 4 respiration in both IMF and SS mitochondria, with the contribution being greater in the IMF subfraction. In addition, the contradiction between human and rat training studies with respect to UCP3 protein expression may partly be explained by the greater than twofold difference in mitochondrial UCP3 content between rat and human skeletal muscle. skeletal muscle; exercise; mitochondria; uncoupling protein-3

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Section: Discussioncontrasting

confidence: 99%

Section: Resultssupporting

confidence: 92%

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Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis

Ljubicic

Adhihetty²,

Hood³

2004

Journal of Applied Physiology

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“…Hind leg muscles were rapidly removed and used for the preparation of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, as described previously (14). Immediately after the isolation, aliquots of mitochondria were frozen and stored at Ϫ80°C for the determination of uncoupling protein 3 (UCP3) by Western blotting using UCP3 antibody (Chemicon International, Temecula, CA), as previously described (15,16). Measurements of mitochondrial respiration and basal and palmitateinduced proton leak.…”

Section: Methodsmentioning

confidence: 99%

Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction

et al. 2006

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An accelerated rate of fat recovery (catch-up fat) and insulin resistance are characteristic features of weight recovery after caloric restriction, with implications for the pathophysiology of catch-up growth and weight fluctuations. Using a previously described rat model of weight recovery in which catch-up fat and skeletal muscle insulin resistance have been linked to suppressed thermogenesis per se, we investigated alterations in mitochondrial energetics and oxidative stress in subsarcolemmal (SS) and intermyofibrillar (IMF) skeletal muscle mitochondria. After 2 weeks of semistarvation followed by 1 week of refeeding, the refed rats show persistent and selective reductions in SS mitochondrial mass (assessed from citrate synthase activity in tissue homogenate and isolated mitochondria) and oxidative capacity. Furthermore, the refed rats show, in both SS and IMF muscle mitochondria, a lower aconitase activity (whose inactivation is an index of increased reactive oxygen species [ROS]), associated with higher superoxide dismutase activity and increased proton leak. Taken together, these studies suggest that diminished skeletal muscle mitochondrial mass and function, specifically in the SS mitochondrial compartment, contribute to the high metabolic efficiency for catch-up fat after caloric restriction and underscore a potential link between diminished skeletal muscle SS mitochondrial energetics, increased ROS concentration, and insulin resistance during catch-up fat. Diabetes

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“…This hypothesis of a UCP-mediated state of partial uncoupling in fasted muscle is, however, at odds to that expected for any putative mediator of thermogenesis in a well-established condition of energy conservation at the whole body level [41] and in the skeletal muscle [57]. In particular, fastinginduced increases in UCP2 and UCP3 expressions in skeletal muscle occur without changes in kinetics of proton conductance pathway in isolated mitochondria [58,59] and without changes in the overall state of mitochondrial energy coupling in the hindlimb of awake animals, as assessed by noninvasive 13C/31P NMR spectroscopic approaches [60]. (iii) High-fat feeding paradox: Similarly in humans, increasing fat in the diet leads to increased skeletal muscle UCP3 expression but not in mitochondrial uncoupling, as assessed by the lack of any changes in the rate of muscle phosphocreatine resynthesis during conditions of maximal flux through oxidative phosphorylation [61].…”

Section: Ucp1-homologues: Are They Mediators Of Thermogenesis?mentioning

confidence: 96%

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Dulloo

Seydoux

Jacquet

2004

Physiology & Behavior

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After decades of controversies about the quantitative importance of autoregulatory adjustments in energy expenditure in weight regulation, there is now increasing recognition that even subtle variations in thermogenesis could, in dynamic systems and over the long term, be important in determining weight maintenance in some and obesity in others. The main challenge nowadays is to provide a mechanistic explanation for the role of adaptive thermogenesis in attenuating and correcting deviations of body weight and body composition, and in the identification of molecular mechanisms that constitute its effector systems. This workshop paper reconsiders what constitutes adaptive changes in thermogenesis and reassesses the role of the sympathetic nervous system (SNS) and uncoupling proteins (UCP1, UCP2, UCP3, UCP5/BMCP1) as the efferent and effector components of the classical one-control system for adaptive thermogenesis and fat oxidation. It then reviews the evidence suggesting that there are in fact two distinct control systems for adaptive thermogenesis, the biological significance of which is to satisfy-in a lifestyle of famine-and-feast-the needs to suppress thermogenesis for energy conservation during weight loss and weight recovery even under environmental stresses (e.g., cold, infection, nutrient imbalance) when sympathetic activation of thermogenesis has equally important survival value.Keywords: Obesity; Diabetes; Cachexia; Catecholamines; UCP Resistance to obesity in an obesigenic environmentOne of the greatest challenges towards understanding the aetiology of human obesity is to explain how in environments that promote overeating of high-fat foods and discourage physical activity, there is always a section of the population who, apparently without conscious effort, do not become obese. How do they resist obesity? How is constancy of body weight achieved over decades in these individuals? In addressing the issue of human susceptibility to leanness and fatness, there are three cardinal features of body weight regulation that need to be underlined: (i) Humans cannot escape the laws of thermodynamics.Whatever theory is put forward to explain body weight and body composition regulation, it is undeniable that changes in body energy stores (and ultimately body weight) cannot occur unless there is a difference between energy intake and energy expenditure. (ii) Subtle perturbations in energy balance can lead to obesity. To put it another way, long-term constancy of body weight can only be achieved if the matching between energy intake and energy expenditure is extremely precise, since an error of only 1% between input and output of energy, if persistent, will lead to a gain or loss of 1 kg per year or some 40 kg between the age of 20 to 60 years. Yet, a difference of 5% between energy intake and energy expenditure is hardly measurable with available techniques. (iii) Body weight is a fluctuating and oscillatory phenomenon. Even in individuals that maintain a relatively stable lean body weight over decades, the...

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Differences in proton leak kinetics, but not in UCP3 protein content, in subsarcolemmal and intermyofibrillar skeletal muscle mitochondria from fed and fasted rats

Cited by 21 publications

References 35 publications

Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis

Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis

Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

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