Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle

Fernström, Maria; Tonkonogi, Michail; Sahlin, Kent

doi:10.1113/jphysiol.2003.055202

Cited by 126 publications

(130 citation statements)

References 41 publications

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“…However, previous studies have shown a strong correlation between citrate synthase activity and VO 2max (37), and, in our study, citrate synthase activity in type 2 diabetic patients and control subjects was in fact similar. Furthermore, several studies have shown that physical training does not affect measures of respiration per mitochondrion when using pyruvate and palmitoyl-L-carnitine plus malate as substrates (24,25,38). Finally, the values of state 3 respiration with pyruvate plus malate observed in the sedentary, obese, nondiabetic subjects in the present study were similar to those previously reported in young healthy trained and untrained subjects (38,39).…”

Section: Discussionsupporting

confidence: 81%

Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

et al. 2007

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We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADPstimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were no differences in respiration with palmitoyl-Lcarnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance (P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes in humans with obesity. Diabetes 56:1592-1599, 2007 T ype 2 diabetes is characterized by insulin resistance in major metabolic tissues such as skeletal muscle, liver, and adipose tissue, as well as failure of the pancreatic ␤-cells to compensate for this abnormality (1). Skeletal muscle is the major site of glucose disposal in response to insulin and, correspondingly, the major site of insulin resistance in type 2 diabetes (1,2). Despite extensive research, the mechanisms underlying insulin resistance are not fully understood. Indeed, several abnormalities have been identified in insulinresistant muscle including impaired insulin activation of glycogen synthase (1,3), impairment of the proximal components of the insulin signaling cascade (2), and increased intramuscular triglyceride content (4,5). Another important component of insulin resistance appears to be a decreased ability of insulin to regulate fuel utilization (6 -8). In insulin-resistant subjects, this impaired ability to switch from lipid to carbohydrate oxidation in response to insulin has been described as "metabolic inflexibility" of skeletal muscle (8).Being the site of fuel oxidation, the mitochondrion has gained increasing interest in type 2 diabetes research during the last decade. Several studies have indicated a role for mitochondrial dysfunction in the pathogenesis of insulin resistance and type 2 diabetes. This includes reports of a decreased leg lipid oxidation in type 2 diabetes and obesity (9) and a strong neg...

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Section: Discussionsupporting

confidence: 81%

Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

et al. 2007

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“…2C). The contractile activity-induced adaptations of UCP3 seen in the present study, along with the results of Jones et al (33), who used swim training in rodents, are in contrast to the findings of studies using human subjects (16,41,46) that show a decreased UCP3 protein content after endurance training. Indeed, inspection of the literature reveals marked differences in the expression of UCP3 between rodents and humans in response to identical physiological conditions ( Table 1).…”

Section: Discussioncontrasting

confidence: 57%

“…The role of UCP3 in the regulation of mitochondrial state 4 respiration has also been the subject of considerable debate (7,9,34,38). In addition, the nature of the adaptation of this protein to stressors such as chronic physical activity remains contested (16,33,41,46). Therefore, the main purposes of the present study were to characterize UCP3 protein content and function in skeletal muscle IMF and SS mitochondria and to relate chronic contractile activity-induced adaptations in UCP3 content to state 4 respiration in the mitochondrial subfractions.…”

Section: Discussionmentioning

confidence: 99%

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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“…Indeed, our exercise protocol was not enough to produce the same metabolic muscular changes observed in trained animals. It is well known that endurance training causes an increase in the activity of oxidative enzymes (14,22,23). One of these enzymes is the citrate synthase, which is localized on the inner mitochondrial membrane and promotes the condensation of acetyl-CoA and oxalacetate, generating citrate in the Krebs cycle (36,48).…”

Section: Discussionmentioning

confidence: 99%

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Ogihara

Schoorlemmer

Levada

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Ogihara CA, Schoorlemmer GHM, Levada AC, Pithon-Curi TC, Curi R, Lopes OU, Colombari E, Sato MA. Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 299: R291-R297, 2010. First published April 21, 2010 doi:10.1152/ajpregu.00055.2009.-Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. The purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. The day after the last exercise session, the rats were anesthetized with intravenous ␣-chloralose, tracheostomized, and artificially ventilated. The femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (Ϫ25 Ϯ 6 and Ϫ30 Ϯ 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 Ϯ 8 vs. 24 Ϯ 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (Ϫ20 Ϯ 4 and Ϫ16 Ϯ 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 Ϯ 2% vs. 19 Ϯ 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.GABA; cardiovascular; citrate synthase THE NUCLEUS OF THE SOLITARY tract (NTS) is the primary site in the central nervous system that receives the afferents arising from arterial baro-and chemoreceptors (10, 15). The intermediate NTS receives inputs particularly from arterial baroreceptors, but some of these afferents achieve the commNTS (10, 16). The commNTS also receives inputs from arterial chemoreceptors, and seems to be highly sensitive to carotid chemoreceptor stimulation (8, 9, 11).The possible role of the commNTS as a source of sympathoexcitation was first shown by Nelson et al. (33), which demonstrated that nanoliter injections of L-glutamate into the commNTS evoke elevations in heart rate and arterial pressure mediated by the sympathetic nervous system. Electrolytic lesions or chemical inhibition of the commNTS have been shown to markedly decrease the splanchnic sympathetic nerve activity and arterial pressure in spontaneously hypertensive rats (SHR), which suggested that this subnucleus of the NTS contains neurons tonically active in S...

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Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle

Cited by 126 publications

References 41 publications

Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

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

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

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