Biomedical subjects

Peter Schjerling

Publications and source records attributed to Peter Schjerling.

22 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↗

PubMed2002

Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture.

Activation of either the calcineurin or the extracellular signal-regulated kinase (ERK1/2) pathway increases the percentage of slow fibres in vivo suggesting that both pathways can regulate fibre phenotypes in skeletal muscle. We investigated the effect of calcineurin blockade with cyclosporin A and mitogen-activated protein kinase kinase (MEK1/2) blockade with U0126 upon myosin heavy chain (MHC) isoform mRNA levels and activities of metabolic enzymes after 1 day, 3 days and 7 days of treatment in primary cultures of spontaneously twitching rat skeletal muscle. U0126 treatment significantly decreased MHC Ibeta mRNA levels and significantly increased MHC IIX, MHC IIB, embryonal MHC and perinatal MHC mRNA levels when compared to control. In addition, U0126 treatment significantly increased lactate dehydrogenase, creatine kinase, hexokinase, malate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase activities above control values while a significant reduction in the percentage of pyruvate dehydrogenase in the active form was also observed. Calcineurin blockade significantly decreased both MHC Ibeta and embryonal mRNA levels below control and significantly increased MHC IIX mRNA levels. Significant increases in the activities of both lactate dehydrogenase and creatine kinase above control values were also seen following cyclosporin A treatment. In conclusion, the results suggest that calcineurin upregulates slow-fibre genes and suppresses fast-fibre genes. Similarly, the ERK1/2 pathway upregulates slow-fibre MHC and suppresses fast-fibre MHC isoforms. However, the effect on enzyme activities is not fibre-type specific. The effect of U0126 on the percentage of pyruvate dehydrogenase in the active form suggests that the ERK1/2 pathway may also be involved in regulation of the phosphorylation state of this enzyme.

Animals↗

PubMed2002

Gene gun bombardment-mediated expression and translocation of EGFP-tagged GLUT4 in skeletal muscle fibres in vivo.

Cellular protein trafficking has been studied to date only in vitro or with techniques that are invasive and have a low time resolution. To establish a gentle method for analysis of glucose transporter-4 (GLUT4) trafficking in vivo in fully differentiated rat skeletal muscle fibres we combined the enhanced green fluorescent protein (EGFP) labelling technique with physical transfection methods in vivo: intramuscular plasmid injection or gene gun bombardment. During optimisation experiments with plasmid coding for the EGFP reporter alone EGFP-positive muscle fibres were counted after collagenase treatment of in vivo transfected flexor digitorum brevis (FDB) muscles. In contrast to gene gun bombardment, intramuscular injection produced EGFP expression in only a few fibres. Regardless of the transfection technique, EGFP expression was higher in muscles from 2-week-old rats than in those from 6-week-old rats and peaked around 1 week after transfection. The gene gun was used subsequently with a plasmid coding for EGFP linked to the C-terminus of GLUT4 (GLUT4-EGFP). Rats were anaesthetised 5 days after transfection and insulin given i.v. with or without accompanying electrical hindleg muscle stimulation. After stimulation, the hindlegs were fixed by perfusion. GLUT4-EGFP-positive FDB fibres were isolated and analysed by confocal microscopy. The intracellular distribution of GLUT4-EGFP under basal conditions as well as after translocation to the plasma membrane in response to insulin, contractions, or both, was in accordance with previous studies of endogenous GLUT4. Finally, GLUT4-EGFP trafficking in quadriceps muscle in vivo was studied using time-lapse microscopy analysis in anaesthetised mice and the first detailed time-lapse recordings of GLUT4-EGFP translocation in fully differentiated skeletal muscle in vivo were obtained.

Animals↗

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↗