Biomedical subjects

Adam Steensberg

Publications and source records attributed to Adam Steensberg.

28 records · Page 2Linked to original sources

PubMed2003

Interleukin-6 stimulates lipolysis and fat oxidation in humans.

Although IL-6 is a key modulator of immune function, it also plays a role in regulating substrate metabolism. To determine whether IL-6 affects lipid metabolism, 18 healthy men were infused for 3 h with saline (Con; n = 6) or a high dose (High-rhIL6; n = 6) or a low dose (Low-rhIL6; n = 6) of recombinant human IL-6 (rhIL-6). The IL-6 concentration during Con, Low-rhIL6, and High-rhIL6 was at a steady state after 30 min of infusion at approximately 4, 140, and 320 pg/ml, respectively. Either dose of rhIL-6 was associated with a similar increase in fatty acid (FA) concentration and endogenous FA rate of appearance (R(a)) from 90 min after the start of the infusion. The FA concentration and FA R(a) continued to increase until the cessation of rhIL-6 infusion, reaching levels approximately 50% greater than Con values. The elevated levels reached at the end of rhIL-6 infusion persisted at least 3 h postinfusion. Triacylglycerol concentrations were unchanged during rhIL-6 infusion, whereas whole body fat oxidation increased after the second hour of rhIL-6 infusion. Of note, during Low-rhIL6, the induced elevation in FA concentration and FA R(a) occurred in the absence of any change in adrenaline, insulin, or glucagon, and no adverse side effects were observed. In conclusion, the data identify IL-6 as a potent modulator of fat metabolism in humans, increasing fat oxidation and FA reesterification without causing hypertriacylglyceridemia.

Adult↗

PubMed2003

The role of IL-6 in exercise-induced immune changes and metabolism.

Cytokines such as interleukin (IL)-6 are proteins, which were originally discovered within the immune system. Recent studies, however, demonstrate that IL-6 is produced by, and released from contracting skeletal muscles during exercise. This release occurs in the absence of muscle damage and is related to both contraction per se and low muscle glycogen. IL-6 seems to work as an energy sensor within the muscle cells. Other organs also release IL-6 during exercise; however, muscle-derived IL-6 seems to play an important role in signalling between the muscles and other organs in order to maintain energy supply. IL-6 can enhance lipolysis in humans and might play a role in glucose metabolism. In addition, muscle-derived IL-6 is likely to initiate many of the exercise associated immune changes, as IL-6 can increase plasma levels of the cytokines IL-1 ra and IL-10, together with cortisol and blood neurtrophils. Also, the observed shift towards Th2 lymphocyte dominance during exercise may be mediated by IL-6. Because carbohydrate ingestion during exercise has been demonstrated to blunt the IL-6 and hormonal response, it might also blunt other beneficial adaptations. This review discusses the possible beneficial biological role of high plasma levels of IL-6 during exercise.

Animals↗

PubMed2002

Exercise induces hepatosplanchnic release of heat shock protein 72 in humans.

Physical exercise results in the appearance of heat shock protein (HSP) 72 in the circulation that precedes any increase in gene or protein expression in contracting skeletal muscle. In rodents, exercise increases liver HSP72 expression and the hepatosplanchnic viscera are known to release many acute phase proteins. In the present study, we tested the hypothesis that the splanchnic tissue beds release HSP72 during exercise. Seven male subjects performed 120 min of semi-recumbent cycling at 62 +/- 2 % of maximal oxygen uptake. Blood samples were obtained simultaneously from a brachial artery, a femoral vein and the hepatic vein prior to and at 30, 60 and 120 min of exercise. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and hepatosplanchnic blood flow (HBL) was measured using indocyanine green dye. Net leg and net hepatosplanchnic HSP72 balance were calculated as the product of LBF and femoral venous-arterial HSP72 difference and the product of HBF and hepatic venous-arterial HSP72 difference, respectively. Arterial plasma HSP72 was only detected in one subject at rest but progressively appeared in the arterial samples throughout exercise such that at 120 min it was detected in all subjects (0.88 +/- 0.35 pg l(-1); P < 0.05 compared with rest). The contracting muscle did not, however, contribute to this increase since there was no difference in the femoral venous-arterial HSP72 concentration at any time. Rather, the increase in arterial HSP72 was accounted for, at least in part, by release from the hepatosplanchnic viscera with values increasing (P < 0.05) from undetectable levels at rest to 5.2 +/- 0.2 pg min(-1) after 120 min. These data demonstrate that the splanchnic tissues release HSP72 during exercise and this release is responsible, in part, for the elevated systemic concentration of this protein during exercise.

Adult↗

PubMed2002

IL-6 activates HSP72 gene expression in human skeletal muscle.

To determine whether the cytokine interleukin (IL)-6 induces heat shock protein (HSP) 72 gene expression in skeletal muscle, 18 healthy, young men had either a high dose of IL-6 (HiIL-6; n=6), low dose IL-6 (LoIL-6; n=6), or saline (CON; n=6) infused into one femoral artery for 3h. Muscle biopsies were obtained from the vastus lateralis of the infusion limb and samples were analyzed for HSP72 mRNA. In addition, blood samples were collected from the femoral vein of the infusion limb and analyzed for plasma IL-6. In CON, femoral vein IL-6 concentration remained at basal levels throughout the experiment but in both HiIL-6 and LoIL-6, femoral vein IL-6 concentrations were markedly elevated (P<0.05). HSP72 gene expression did not increase above resting levels in CON. In contrast, in both HiIL-6 and LoIL-6, HSP72 mRNA increased (P<0.05) 2.5- and 2.3-fold, respectively after 30min of infusion and remained elevated (P<0.05) for 24h following infusion. These data demonstrate that IL-6 can rapidly induce HSP72 gene expression in human skeletal muscle.

Gene Expression↗

PubMed2002

IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle.

The aim of the present study was to examine whether IL-6 and TNF-alpha are expressed in, and released from, human skeletal muscle during exercise. We hypothesized that the skeletal muscle will release IL-6, but not TNF-alpha, during exercise because of previous observations that TNF-alpha negatively affects glucose uptake in skeletal muscle. Six healthy, male subjects performed 180 min of two-legged knee-extensor exercise. Muscle samples were obtained from the vastus lateralis of one limb. In addition, blood samples were obtained from a femoral artery and vein. Plasma was analyzed for IL-6 and TNF-alpha. We detected both IL-6 and TNF-alpha mRNA in resting muscle samples, and whereas IL-6 increased (P < 0.05) approximately 100-fold throughout exercise, no significant increase in TNF-alpha mRNA was observed. Arterial plasma TNF-alpha did not increase during exercise. Furthermore, there was no net release of TNF-alpha either before or during exercise. In contrast, IL-6 increased throughout exercise in arterial plasma, and a net IL-6 release from the contracting limb was observed after 120 min of exercise (P < 0.05).

Adult↗

PubMed2002

Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation.

There are many factors that can influence glucose uptake by contracting skeletal muscle during exercise and although one may be intramuscular glycogen content, this relationship is at present not fully elucidated. To test the hypothesis that muscle glycogen concentration influences glucose uptake during exercise, 13 healthy men were studied during two series of experiments. Seven men completed 4 h of two-legged knee extensor exercise 16 h after reducing of muscle glycogen by completing 60 min of single-legged cycling (Series 1). A further six men completed 3 h of two-legged knee extensor exercise on two occasions: one after 60 min of two-legged cycling (16 h prior to the experimental trial) followed by a high carbohydrate diet (HCHO) and the other after the same exercise followed by a low carbohydrate diet (LCHO) (Series 2). Muscle glycogen was decreased by 40 % when comparing the pre-exercised leg (EL) with the control leg (CL) prior to exercise in Series 1. In addition, muscle glycogen was decreased by the same magnitude when comparing LCHO with HCHO in Series 2. In Series 1, glucose uptake was 3-fold higher in the first 60 min of exercise, in the presence of unchanged pre-exercise GLUT4 protein in EL compared with CL, suggesting that the lower glycogen, and not the exercise the day before, might have provided the stimulus for increased glucose uptake. Despite the same magnitude of difference in pre-exercise glycogen concentration when comparing Series 1 with Series 2, neither direct-nor isotopic tracer-determined glucose uptake was higher in LCHO compared with HCHO in Series 2. However, arterial concentrations of insulin and glucose were lower, while free fatty acids and adrenaline were higher in LCHO compared with HCHO. These data suggest that pre-exercise glycogen content may influence glucose uptake during subsequent exercise. However, this is only the case when delivery of substrates and hormones remains constant. When delivery of substrates and hormones is altered, the potential effect of glycogen on glucose uptake is negated.

Adult↗

PubMed2002

Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes.

Transcription of metabolic genes is transiently induced during recovery from exercise in skeletal muscle of humans. To determine whether pre-exercise muscle glycogen content influences the magnitude and/or duration of this adaptive response, six male subjects performed one-legged cycling exercise to lower muscle glycogen content in one leg and then, the following day, completed 2.5 h low intensity two-legged cycling exercise. Nuclei and mRNA were isolated from biopsies obtained from the vastus lateralis muscle of the control and reduced glycogen (pre-exercise glycogen = 609 +/- 47 and 337 +/- 33 mmol kg(-1) dry weight, respectively) legs before and after 0, 2 and 5 h of recovery. Exercise induced a significant (P < 0.05) increase (2- to 3-fold) in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) genes in the reduced glycogen leg only. Although PDK4, lipoprotein lipase (LPL) and hexokinase II (HKII) mRNA were elevated in the reduced glycogen leg before exercise, no consistent difference was found between the two legs in response to exercise. In a second study, six subjects completed two trials (separated by 2 weeks) consisting of 3 h of two-legged knee extensor exercise with either control (398 +/- 52 mmol kg(-1) dry weight) or low (240 +/- 38 mmol kg(-1) dry weight) pre-exercise muscle glycogen. Exercise induced a significantly greater increase in PDK4 transcription in the low glycogen (> 6-fold) than in the control (< 3-fold) trial. Induction of PDK4 and UCP3 mRNA in response to exercise was also significantly higher in the low glycogen (11.4- and 3.5-fold, respectively) than in the control (5.0- and 1.7-fold, respectively) trial. These data indicate that low muscle glycogen content enhances the transcriptional activation of some metabolic genes in response to exercise, raising the possibility that signalling mechanisms sensitive to glycogen content and/or FFA availability may be linked to the transcriptional control of exercise-responsive genes.

Adult↗

PubMed2002

Prolonged exercise, lymphocyte apoptosis and F2-isoprostanes.

Exercise induces a post-exercise decline in the number of circulating lymphocytes. The aim of the present study was to investigate whether strenuous exercise induces lymphocyte apoptosis and generation of reactive oxygen species. Eleven healthy male subjects exercised for 2.5 h on a treadmill. Apoptotic lymphocytes were defined by being annexin positive and 7-aminoactinomycin-D negative. Measurement of F(2)-isoprostanes was used as a marker of oxidant stress in vivo. An increase (60%, P<0.05) in the percentage of apoptotic circulating lymphocytes was found 2 h post-exercise, whereas the total number of apoptotic cells did not change in relation to exercise. The concentration of plasma F(2)-isoprostanes increased approximately 1.6-fold in response to exercise, but declined towards pre-exercise values within the 1st h of recovery. The plasma concentrations of adrenaline, noradrenaline and cortisol increased during exercise. In conclusion, the results of the present study demonstrate that even in a study design in which high levels of apoptosis-inducing factors are generated, such as cortisol and isoprostanes, lymphocyte apoptosis does not contribute to post-exercise lymphocytopenia.

Adult↗

PubMed2002

Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle.

To test the hypothesis that a decrease in intramuscular glycogen availability may stimulate heat shock protein expression, seven men depleted one leg of muscle glycogen the day before performing 4-5 h of exhaustive, two-legged knee extensor exercise at 40 % of leg peak power output. Subjects then rested for a further 3 h. Muscle biopsies were obtained from the depleted and control leg before, immediately after and 3 h into recovery from exercise. These samples were analysed for muscle glycogen, and HSP72 gene and protein expression. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery for the measurement of arterial-venous differences in serum HSP72. Plasma creatine kinase (CK) was also measured from arterial blood samples. Pre-exercise muscle glycogen content was 40 % lower in the depleted compared with the control leg and this difference was maintained throughout the experiment (P < 0.05; main treatment effect). Neither HSP72 gene nor protein expression was different pre-exercise. However, both HSP72 gene and protein increased (P < 0.05) post-exercise in the depleted leg, but not in the control leg. Exercise did not increase plasma CK concentrations and we were unable to detect HSP72 in the serum of any samples. These results demonstrate that while acute, concentric exercise is capable of increasing HSP72 in human skeletal muscle, it does so only when glycogen is reduced to relatively low levels. Hence, our data suggest that HSP72 protein expression is related to glycogen availability. In addition, because CK did not increase and we found no evidence of HSP72 in the venous effluent, our data suggest that skeletal muscle is impermeable to HSP72.

Adult↗

PubMed2002

Exercise and hypoxia: effects on leukocytes and interleukin-6-shared mechanisms?

Stress-induced immunological reactions to exercise have stimulated much research into stress immunology and neuroimmunology. It has been suggested that exercise can be employed as a model of temporary immunosuppression, which occurs during physical stress, such as hypoxia. Acute exercise and acute hypoxia mediate in principle identical effects on circulating lymphocyte and neutrophil numbers. Thus, during exercise and hypoxia, lymphocytes are recruited to the blood. After the stress, the number of lymphocytes declines after the stress, whereas the neutrophil number continues to increase. When exercise is performed during hypoxia, the exercise-induced immune changes are pronounced. There is some evidence that the exercise- and hypoxia-induced changes in leukocyte subpopulations are mediated by neuroendocrinological factors such as catecholamines, growth hormone, and cortisol. In contrast, although exercise, as well as hypoxia, is associated with increased plasma levels of IL-6, the mechanisms are not likely to be the same. Thus, during exercise, contracting skeletal muscles are the main source of IL-6 production, whereas the source of IL-6 during hypoxia has not been demonstrated. The increased level of adrenaline contributes to the enormous increase in plasma IL-6 only to a minor degree during strenuous exercise. However, the only modest increase in IL-6 during hypoxia may be linked to hormonal changes, whereas the prolonged increase in IL-6 during chronic hypoxia is likely to be multifactorial.

Cell Hypoxia↗