Skeletal muscle IL-6 and regulation of liver metabolism during high-fat diet and exercise training

Altres ajuts: The study was supported by grants from the Lundbeck Foundation, The Danish Research Foundation, The Danish Council for Independent Research in the Natural Sciences, and The Augustinus Foundation. Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (#02-512-55).Interleukin ()-6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM -6 is involved in the regulation of exercise training-induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high-fat diet () feeding. Male SkM-specific -6 () and Floxed mice were subjected to Chow diet, or combined with exercise training ( ExTr) for 16 weeks. Hepatic phosphoenolpyruvate carboxykinase () protein content decreased with both and ExTr in Floxed mice, but increased in -6 mice on . In addition, the intrahepatic glucose concentration was in -6 mice higher in than chow. Within ExTr mice, hepatic glucose-6-phosphatase (G6Pase) 36 a protein content was higher in -6 than Floxed mice. Hepatic pyruvate dehydrogenase kinase () 4 and 2 protein content was in Floxed mice lower in ExTr than Chow. In addition, hepatic 1-phosphorylation was higher and 1 protein lower in . Together this suggests that SkM -6 regulates hepatic glucose metabolism, but does not seem to be of major importance for the regulation of oxidative capacity or lipogenesis in liver during or combined with exercise training

Skeletal muscle -6 and regulation of liver metabolism during high-fat diet and exercise training

Altres ajuts: The study was supported by grants from the Lundbeck Foundation, The Danish Research Foundation, The Danish Council for Independent Research in the Natural Sciences, and The Augustinus Foundation. Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (#02-512-55).Interleukin ()-6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM -6 is involved in the regulation of exercise training-induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high-fat diet () feeding. Male SkM-specific -6 () and Floxed mice were subjected to Chow diet, or combined with exercise training ( ExTr) for 16 weeks. Hepatic phosphoenolpyruvate carboxykinase () protein content decreased with both and ExTr in Floxed mice, but increased in -6 mice on . In addition, the intrahepatic glucose concentration was in -6 mice higher in than chow. Within ExTr mice, hepatic glucose-6-phosphatase (G6Pase) 36 a protein content was higher in -6 than Floxed mice. Hepatic pyruvate dehydrogenase kinase () 4 and 2 protein content was in Floxed mice lower in ExTr than Chow. In addition, hepatic 1-phosphorylation was higher and 1 protein lower in . Together this suggests that SkM -6 regulates hepatic glucose metabolism, but does not seem to be of major importance for the regulation of oxidative capacity or lipogenesis in liver during or combined with exercise training

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 2½ h 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 α 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 (P < 0.05) and the LPS (0.05 ≤ P < 0.1) 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 (P < 0.05) PDH and increased (P < 0.05) AMPK and ACC phosphorylation as well as increased (P < 0.05) 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