21 research outputs found
Effects of IL-6 on pyruvate dehydrogenase regulation in mouse skeletal muscle
Skeletal muscle regulates substrate choice according to demand and availability and pyruvate dehydrogenase (PDH) is central in this regulation. Circulating interleukin (IL)-6 increases during exercise and IL-6 has been suggested to increase whole body fat oxidation. Furthermore, IL-6 has been reported to increase AMP-activated protein kinase (AMPK) phosphorylation and AMPK suggested to regulate PDHa activity. Together, this suggests that IL-6 may be involved in regulating PDH. The aim of this study was to investigate the effect of a single injection of IL-6 on PDH regulation in skeletal muscle in fed and fasted mice. Fed and 16â18 h fasted mice were injected with either 3 ngâ¡âg(â1) recombinant mouse IL-6 or PBS as control. Fasting markedly reduced plasma glucose, muscle glycogen, muscle PDHa activity, as well as increased PDK4 mRNA and protein content in skeletal muscle. IL-6 injection did not affect plasma glucose or muscle glycogen, but increased AMPK and ACC phosphorylation and tended to decrease p38 protein content in skeletal muscle in fasted mice. In addition IL-6 injection reduced PDHa activity in fed mice and increased PDHa activity in fasted mice without significant changes in PDH-E1Îą phosphorylation or PDP1 and PDK4 mRNA and protein content. The present findings suggest that IL-6 contributes to regulating the PDHa activity and hence carbohydrate oxidation, but the metabolic state of the muscle seems to determine the outcome of this regulation. In addition, AMPK and p38 may contribute to the IL-6-mediated PDH regulation in the fasted state
Regulation of PDH, GS and insulin signalling in skeletal muscle: effect of physical activity level and inflammation
Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver
Effects of exercise training on regulation of skeletal muscle glucose metabolism in elderly men
Exercise-induced AMPK and pyruvate dehydrogenase regulation is maintained during short-term low-grade inflammation
The aim of the present study was to examine the effect of lipopolysaccharide (LPS)-induced inflammation on AMP-activated protein kinase (AMPK) and pyruvate dehydrogenase (PDH) regulation in human skeletal muscle at rest and during exercise. Nine young healthy physically inactive male subjects completed two trials. In an LPS trial, the subjects received a single LPS injection (0.3 ng/kg body weight) and blood samples and vastus lateralis muscle biopsies were obtained before and 2 h after the LPS injection and immediately after a 10-min one-legged knee extensor exercise bout performed approximately 2½âh after the LPS injection. The exercise bout with muscle samples obtained before and immediately after was repeated in a control trial without LPS injection. The plasma tumor necrosis factor Îą concentration increased 17-fold 2 h after LPS relative to before. Muscle lactate and muscle glycogen were unchanged from before to 2 h after LPS and exercise increased muscle lactate and decreased muscle glycogen in the control (Pâ<â0.05) and the LPS (0.05ââ¤âPâ<â0.1) trial with no differences between the trials. AMPK, acetyl-CoA carboxylase (ACC) and PDH phosphorylation as well as PDHa activity were unaffected 2 h after LPS relative to before. Exercise decreased (Pâ<â0.05) PDH and increased (Pâ<â0.05) AMPK and ACC phosphorylation as well as increased (Pâ<â0.05) PDHa activity similarly in the LPS and control trial. In conclusion, LPS-induced inflammation does not affect resting or exercise-induced AMPK and PDH regulation in human skeletal muscle. This suggests that metabolic flexibility during exercise is maintained during short-term low-grade inflammation in humans
Effects of Exercise Training on Regulation of Skeletal Muscle Glucose Metabolism in Elderly Men
Reply from Lasse Gliemann, Jesper Olesen, Rasmus Sjørup Biensø, Stefan Peter Mortensen, Michael Nyberg, Jens Bangsbo, Henriette Pilegaard and Ylva Hellsten
5´AMP activated protein kinase ι2 controls substrate metabolism during post-exercise recovery via regulation of pyruvate dehydrogenase kinase 4
KEY POINTS: There is lower fat oxidation during postâexercise recovery in mice lacking 5â˛âAMP activated protein kinase Îą(2) (AMPKÎą(2)). AMPKÎą(2) is involved in postâtranscriptional and not transcriptional regulation of pyruvate dehydrogenase kinase 4 (PDK4) in muscle. Exerciseâinduced AMPKÎą(2) activity increases PDK4 protein content, in turn inhibiting pyruvate dehydrogenase activity and glucose oxidation. The mechanism for increased postâexercise fat oxidation is by inhibition of carbohydrate oxidation allowing increased fat oxidation rather than by direct stimulation of fat oxidation. ABSTRACT: It is well known that exercise has a major impact on substrate metabolism for many hours after exercise. However, the regulatory mechanisms increasing lipid oxidation and facilitating glycogen resynthesis in the postâexercise period are unknown. To address this, substrate oxidation was measured after prolonged exercise and during the following 6 h postâexercise in 5´âAMP activated protein kinase (AMPK) Îą(2) and Îą(1) knockâout (KO) and wildâtype (WT) mice with free access to food. Substrate oxidation was similar during exercise at the same relative intensity between genotypes. During postâexercise recovery, a lower lipid oxidation (P < 0.05) and higher glucose oxidation were observed in AMPKÎą(2) KO (respiratory exchange ratio (RER) = 0.84 ¹ 0.02) than in WT and AMPKÎą(1) KO (average RER = 0.80 ¹ 0.01) without genotype differences in muscle malonylâCoA or freeâcarnitine concentrations. A similar increase in muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in WT and AMPKÎą(2) KO was observed following exercise, which is consistent with AMPKÎą(2) deficiency not affecting the exerciseâinduced activation of the PDK4 transcriptional regulators HDAC4 and SIRT1. Interestingly, PDK4 protein content increased (63%, P < 0.001) in WT but remained unchanged in AMPKÎą(2) KO. In accordance with the lack of increase in PDK4 protein content, lower (P < 0.01) inhibitory pyruvate dehydrogenase (PDH)âE1Îą Ser(293) phosphorylation was observed in AMPKÎą(2) KO muscle compared to WT. These findings indicate that AMPKÎą(2) regulates muscle metabolism postâexercise through inhibition of the PDH complex and hence glucose oxidation, subsequently creating conditions for increased fatty acid oxidation