Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

Bertholdt, Lærke; Gudiksen, Anders; Schwartz, Camilla Victoria Lindgren; Knudsen, Janne Lehmann; Pilegaard, Henriette

doi:10.1152/ajpregu.00373.2016

Cited by 14 publications

(10 citation statements)

References 36 publications

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“…Alternatively, hepatic lactate uptake may have been reduced when muscle IL-6 was lacking. However, the higher PEPCK protein content 10h after exercise in both genotypes, without changes in PEPCK mRNA and G6Pase mRNA or protein content, does not support that IL-6 MKO mice had altered gluconeogenic capacity, which is in line with previous studies [ 6 , 39 ]. Thus, the increased plasma lactate concentration in IL-6 MKO than in Control mice may be due to reduction in hepatic lactate uptake, but the similarly reduced liver lactate 6h post exercise in both genotypes seems to indicate that the higher plasma lactate is because of higher peripheral lactate production.…”

Section: Discussionsupporting

confidence: 58%

Skeletal muscle IL-6 regulates muscle substrate utilization and adipose tissue metabolism during recovery from an acute bout of exercise

et al. 2017

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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.

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Section: Discussionsupporting

confidence: 58%

Skeletal muscle IL-6 regulates muscle substrate utilization and adipose tissue metabolism during recovery from an acute bout of exercise

et al. 2017

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“…The brain is another source of IL-6 in circulation during exercise [11,12], and adipose tissue releases IL-6 into the circulation after exercise, but not during exercise [13]. Exercise induces liver IL-6 gene expression [14,15,16], but the liver does not release IL-6 into the circulation [17]. Peritendon tissue also produces IL-6 [18].…”

Section: Introductionmentioning

confidence: 99%

Glucose Ingestion Inhibits Endurance Exercise-Induced IL-6 Producing Macrophage Infiltration in Mice Muscle

Tominaga

Saitou

2019

Nutrients

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Background: Carbohydrate (CHO) supplementation during exercise attenuates exercise-induced increases in plasma Interleukin (IL)-6 concentration. However, the effects of CHO supplementation on muscle IL-6 production during endurance exercise is controversial. The purpose of this study was to investigate the effects of CHO supplementation on muscle IL-6 production during endurance exercise with a special focus on the IL-6 producing cells. Methods: C57BL/6J mice were divided into three groups—sedentary with water ingestion group as the control (Con; n = 10), exercise with water ingestion group (Ex; n = 10), and exercise with 6% glucose ingestion group (Ex + glucose; n = 10). The Ex and Ex + glucose groups completed 3 h of treadmill running (24 m/min, 7% incline) and were sacrificed immediately after exercise. Results: The exercise-induced increases of plasma IL-6 concentration and gastrocnemius IL-6 gene expression were attenuated by glucose ingestion. However, the increases of soleus IL-6 gene expression and gastrocnemius and soleus IL-6 protein expression were not attenuated by glucose ingestion. Furthermore, we observed that macrophages that infiltrated muscle produce IL-6 and glucose ingestion attenuated the infiltration of IL-6-producing macrophages. Conclusion: This study revealed that infiltrating macrophages may be one type of IL-6-producing cells during endurance exercise, and the infiltration of these cells in muscle was attenuated by glucose ingestion. However, the effects of glucose ingestion on muscle IL-6 production were limited.

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“…Accordingly, hepatic phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activity has been shown to increase immediately after exercise in rats [ 8 ]. Moreover, hepatic mRNA and/or protein content of PEPCK and G6Pase have been demonstrated to increase during exercise and fasting in rodents [ 2 , 13 , 19 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

PGC-1α in exercise and fasting-induced regulation of hepatic UPR in mice

Kristensen

Olsen

Jessen

et al. 2018

Pflugers Arch - Eur J Physiol

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The aim of the present study was to test the hypothesis that PGC-1α is involved in the regulation of hepatic UPR and autophagy in response to both exercise and fasting in mice. Liver-specific PGC-1α knockout (LKO) mice and their floxed littermates (lox/lox) were used in two experimental parts. Liver and plasma were obtained from (1) fed and 18 h fasted mice and (2) immediately after, 2, 6, and 10 h after 1-h treadmill running as well as from resting mice, where one resting group was euthanized at time points corresponding to 0 and 2 h and another corresponding to 6 and 10 h of recovery. Hepatic eIF2α phosphorylation and sXBP1 mRNA content increased immediately after exercise and IRE1α phosphorylation as well as cleaved ATF6 protein content was higher 2 h into recovery than at rest in both genotypes. Fasting reduced hepatic IRE1α phosphorylation and protein content as well as PERK protein and sXBP1 mRNA content similarly in lox/lox and LKO mice. In addition, the hepatic LC3II/LC3I protein ratio increased immediately after exercise and with fasting in both genotypes, while fasting decreased p62 protein content in lox/lox mice. Liver-specific PGC-1α knockout did not affect these responses, but the LC3II/LC3I protein ratio was higher in LKO than lox/lox mice in both rest groups. In conclusion, the present study provides evidence for pathway-specific exercise-induced activation and fasting-induced downregulation of the UPR as well as exercise and fasting-induced regulation of autophagy in mouse liver. In addition, overall PGC-1α does not seem to be required for the fasting and exercise-induced regulation of UPR and autophagy, but may be involved in regulating basal hepatic autophagy.

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Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

Cited by 14 publications

References 36 publications

Skeletal muscle IL-6 regulates muscle substrate utilization and adipose tissue metabolism during recovery from an acute bout of exercise

Skeletal muscle IL-6 regulates muscle substrate utilization and adipose tissue metabolism during recovery from an acute bout of exercise

Glucose Ingestion Inhibits Endurance Exercise-Induced IL-6 Producing Macrophage Infiltration in Mice Muscle

PGC-1α in exercise and fasting-induced regulation of hepatic UPR in mice

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