15 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
Skeletal muscle IL-6 regulates muscle substrate utilization and adipose tissue metabolism during recovery from an acute bout of exercise
An acute bout of exercise imposes a major challenge on whole-body metabolism and metabolic adjustments are needed in multiple tissues during recovery to reestablish metabolic homeostasis. It is currently unresolved how this regulation is orchestrated between tissues. This study was undertaken to clarify the role of skeletal muscle derived interleukin 6 (IL-6) in the coordination of the metabolic responses during recovery from acute exercise. Skeletal muscle specific IL-6 knockout (IL-6 MKO) and littermate Control mice were rested or ran on a treadmill for 2h. Plasma, skeletal muscle, liver and adipose tissue were obtained after 6 and 10h of recovery. Non-exercised IL-6 MKO mice had higher plasma lactate and lower plasma non-esterified fatty acids than Controls. The activity of pyruvate dehydrogenase in the active form was, in skeletal muscle, higher in IL-6 MKO mice than Controls in non-exercised mice and 6h after exercise. IL-6 MKO mice had lower glucose transporter 4 protein content in inguinal adipose tissue (WAT) than Control in non-exercised mice and 10h after treadmill running. Epididymal WAT hormone sensitive lipase phosphorylation and inguinal WAT mitogen activated kinase P38 phosphorylation were higher in IL-6 MKO than Control mice 6h after exercise. These findings indicate that skeletal muscle IL-6 may play an important role in the regulation of substrate utilization in skeletal muscle, basal and exercise-induced adaptations in adipose tissue glucose uptake and lipolysis during recovery from exercise. Together this indicates that skeletal muscle IL-6 contributes to reestablishing metabolic homeostasis during recovery from exercise by regulating WAT and skeletal muscle metabolism
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
Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise
Impact of fasting followed by short-term exposure to interleukin-6 on cytochrome P450 mRNA in mice
Beta<sub>2</sub>-agonist increases skeletal muscle interleukin 6 production and release in response to resistance exercise in men
OBJECTIVE: Several tissues produce and release interleukinâ6 (ILâ6) in response to beta(2)âadrenergic stimulation with selective agonists (beta(2)âagonists). Moreover, exercise stimulates muscle ILâ6 production, but whether beta(2)âagonists regulate skeletal muscle production and release of ILâ6 in humans in association with exercise remains to be clarified. Thus, we investigated leg ILâ6 release in response to beta(2)âagonist salbutamol in lean young men at rest and in recovery from resistance exercise. DESIGN: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma ILâ6 as well as femoral artery blood flow was measured before and ½â5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of ILâ6 and Tumor Necrosis Factor (TNF)âÎą. RESULTS: Average leg ILâ6 release was 1.7âfold higher (p = 0.01) for salbutamol than placebo, being 138 ¹ 76 and 79 ¹ 66 pg min(â1) (mean ¹ SD) for salbutamol and placebo, respectively, but ILâ6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle ILâ6 mRNA was 1.5â and 1.7âfold higher (p = 0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNFâÎą mRNA. CONCLUSIONS: Beta(2)âadrenergic stimulation with high doses of the selective beta(2)âagonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of ILâ6 in skeletal muscle in response to resistance exercise, and increases muscle ILâ6 release in lean individuals
Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training
To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6 loxP/loxP (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks. Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK) Thr172 phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK Thr172 and hormone-sensitive lipase (HSL) Ser565 phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1Îą (PDH-E1Îą) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice. These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors
Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver
PGC-1Îą is required for exercise- and exercise training-induced UCP1 up-regulation in mouse white adipose tissue.
The aim of the present study was to test the hypotheses that 1) a single exercise bout increases UCP1 mRNA in both inguinal (i)WAT and epididymal (e)WAT, 2) UCP1 expression and responsiveness to exercise are different in iWAT and eWAT, 3) PGC-1Îą determines the basal levels of UCP1 and PRDM16 in WAT and 4) exercise and exercise training regulate UCP1 and PRDM16 expression in WAT in a PGC-1Îą-dependent manner.Whole body PGC-1Îą knockout (KO) and wildtype (WT) littermate mice performed a single treadmill exercise bout at 14 m/min and 10% slope for 1 hour. Mice were sacrificed and iWAT, eWAT and quadriceps muscle were removed immediately after, 2, 6 and 10 hours after running, and from sedentary mice that served as controls. In addition, PGC-1Îą KO mice and WT littermates were exercise trained for 5 weeks with sedentary mice as untrained controls. Thirty-six-37 hours after the last exercise bout iWAT was removed.UCP1 mRNA content increased 19-fold in iWAT and 7.5-fold in eWAT peaking at 6 h and 0' of recovery, respectively, in WT but with no changes in PGC-1Îą KO mice. UCP1 protein was undetectable in eWAT and very low in iWAT of untrained mice but increased with exercise training to 4.4 (AU) in iWAT from WT mice without significant effects in PGC-1Îą KO mice.The present observations provide evidence that exercise training increases UCP1 protein in iWAT through PGC-1Îą, likely as a cumulative effect of transient increases in UCP1 expression after each exercise bout. Moreover, the results suggest that iWAT is more responsive than eWAT in exercise-induced regulation of UCP1. In addition, as PRDM16 mRNA content decreased in recovery from acute exercise, the present findings suggest that acute exercise elicits regulation of several brown adipose tissue genes in mouse WAT