The role of gp130 receptor cytokines in the regulation of metabolic homeostasis

Cron, Lena; Allen, Tamara L; Febbraio, Mark A.

doi:10.1242/jeb.129213

Cited by 45 publications

(43 citation statements)

References 74 publications

(95 reference statements)

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“…In muscle cells, contraction leads to the activation of the mitogen-activated protein kinase (MAPK) and Janus kinase (JAK)-signal transducers and activators of transcription (STAT) cascade phosphorylation (Wunderlich et al, 2013), ending with IL-6 transcription in skeletal muscle. It is important to note that the IL-6 produced and secreted by skeletal muscle has beneficial effects on metabolism, since this response exerts effects on GLUT4 translocation in the muscle that increases glycogen synthesis, insulin sensitivity in central, and peripheral organs and enhances lipid oxidation in the skeletal muscle (Al-Khalili et al, 2006; Pal et al, 2014; Cron et al, 2016), in order to provide fuel to supply the skeletal muscle during activity.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokines and BDNF Response to High-Intensity Intermittent Exercise: Effect the Exercise Volume

Cabral-Santos¹,

Castrillón²,

Miranda³

et al. 2016

Front. Physiol.

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The purpose of this study was to compare the effects of two similar high-intensity intermittent exercises (HIIE) but different volume 1.25 km (HIIE1.25) and 2.5 km (HIIE2.5) on inflammatory and BDNF responses. Ten physically active male subjects (age 25.22 ± 1.74 years, body mass 78.98 ± 7.31 kg, height 1.78 ± 0.06 m, VO2peak 59.94 ± 9.38 ml·kg·min−1) performed an incremental treadmill exercise test and randomly completed two sessions of HIIE on a treadmill (1:1 min at vVO2max with passive recovery). Blood samples were collected at rest, immediately and 60-min after the exercise sessions. Serum was analyzed for glucose, lactate, IL-6, IL-10, and BDNF levels. Blood lactate concentrations was higher immediately post-exercise compared to rest (HIIE1.25: 1.69 ± 0.26–7.78 ± 2.09 mmol·L−1, and HIIE2.5: 1.89 ± 0.26–7.38 ± 2.57 mmol·L−1, p < 0.0001). Glucose concentrations did not present changes under the different conditions, however, levels were higher 60-min post-exercise than at rest only in the HIIE1.25 condition (rest: 76.80 ± 11.14–97.84 ± 24.87 mg·dL−1, p < 0.05). BDNF level increased immediately after exercise in both protocols (HIIE1.25: 9.71 ± 306–17.86 ± 8.59 ng.mL−1, and HIIE2.5: 11.83 ± 5.82–22.84 ± 10.30 ng.mL−1). Although both exercises increased IL-6, level percent between rest and immediately after exercise was higher in the HIIE2.5 than HIIE1.25 (30 and 10%; p = 0.014, respectively). Moreover, IL-10 levels percent increase between immediately and 60-min post-exercise was higher in HIIE2.5 than HIIE1.25 (37 and 10%; p = 0.012, respectively). In conclusion, both HIIE protocols with the same intensity were effective to increase BDNF and IL-6 levels immediately after exercise while only IL-10 response was related to the durantion of exercise indicanting the importance of this exercise prescription variable.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokines and BDNF Response to High-Intensity Intermittent Exercise: Effect the Exercise Volume

Cabral-Santos¹,

Castrillón²,

Miranda³

et al. 2016

Front. Physiol.

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“…Although chronic inflammation is a non‐specific immune response, cytokines are inflammatory mediators that have been implicated in the progression of several diseases and associated co‐morbidities (Deans & Wigmore, ; Fearon, Glass, & Guttridge, ; Lightfoot & Cooper, ; Zhou, Liu, Liang, Li, & Song, ). In addition to tumour growth and development, elevated circulating IL‐6 has been linked to disrupted protein turnover associated with cancer‐induced muscle wasting (Carson & Baltgalvis, ; Cron, Allen, & Febbraio, ; Narsale & Carson, ). Interleukin‐6 has been shown to regulate skeletal muscle metabolism through the activation of GLUT4 translocation and accelerated lipolysis (Cron et al., ).…”

Section: Discussionmentioning

confidence: 99%

The regulation of skeletal muscle fatigability and mitochondrial function by chronically elevated interleukin‐6

VanderVeen

Fix

Montalvo

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?Interleukin‐6 has been associated with muscle mass and metabolism in both physiological and pathological conditions. A causal role for interleukin‐6 in the induction of fatigue and disruption of mitochondrial function has not been determined. What is the main finding and its importance?We demonstrate that chronically elevated interleukin‐6 increased skeletal muscle fatigability and disrupted mitochondrial content and function independent of changes in fibre type and mass. Abstract Interleukin‐6 (IL‐6) can initiate intracellular signalling in skeletal muscle by binding to the IL‐6‐receptor and interacting with the transmembrane gp130 protein. Circulating IL‐6 has established effects on skeletal muscle mass and metabolism in both physiological and pathological conditions. However, the effects of circulating IL‐6 on skeletal muscle function are not well understood. The purpose of this study was to determine whether chronically elevated systemic IL‐6 was sufficient to disrupt skeletal muscle force, fatigue and mitochondrial function. Additionally, we examined the role of muscle gp130 signalling during overexpression of IL‐6. Systemic IL‐6 overexpression for 2 weeks was achieved by electroporation of an IL‐6 overexpression plasmid or empty vector into the quadriceps of either C57BL/6 (WT) or skeletal muscle gp130 knockout (KO) male mice. Tibialis anterior muscle in situ functional properties and mitochondrial respiration were determined. Interleukin‐6 accelerated in situ skeletal muscle fatigue in the WT, with a 18.5% reduction in force within 90 s of repeated submaximal contractions and a 7% reduction in maximal tetanic force after 5 min. There was no difference between fatigue in the KO and KO+IL‐6. Interleukin‐6 reduced WT muscle mitochondrial respiratory control ratio by 36% and cytochrome c oxidase activity by 42%. Interleukin‐6 had no effect on either KO respiratory control ratio or cytochrome c oxidase activity. Interleukin‐6 also had no effect on body weight, muscle mass or tetanic force in either genotype. These results provide evidence that 2 weeks of elevated systemic IL‐6 is sufficient to increase skeletal muscle fatigability and decrease muscle mitochondrial content and function, and these effects require muscle gp130 signalling.

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“…Elevated circulating IL-6 can be observed in cachectic cancer patients and preclinical models alike and is strongly correlated to body weight and muscle mass loss [44–46]. IL-6 signals through the ubiquitously expressed glycoprotein 130 (gp130) receptor to activate downstream intracellular signaling pathways [42, 47, 48]. While IL-6 can activate numerous cellular signaling pathways, the phosphorylation of immediate downstream target signal transducer and activator of transcription 3 (STAT3) has been most widely examined with cachexia-induced muscle mass loss [41, 49, 50].…”

Section: Overview Of Inflammation As a Driver Of Cancer Cachexiamentioning

confidence: 99%

Disrupted Skeletal Muscle Mitochondrial Dynamics, Mitophagy, and Biogenesis during Cancer Cachexia: A Role for Inflammation

VanderVeen

Fix

Carson

2017

Oxidative Medicine and Cellular Longevity

146

173

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Chronic inflammation is a hallmark of cancer cachexia in both patients and preclinical models. Cachexia is prevalent in roughly 80% of cancer patients and accounts for up to 20% of all cancer-related deaths. Proinflammatory cytokines IL-6, TNF-α, and TGF-β have been widely examined for their regulation of cancer cachexia. An established characteristic of cachectic skeletal muscle is a disrupted capacity for oxidative metabolism, which is thought to contribute to cancer patient fatigue, diminished metabolic function, and muscle mass loss. This review's primary objective is to highlight emerging evidence linking cancer-induced inflammation to the dysfunctional regulation of mitochondrial dynamics, mitophagy, and biogenesis in cachectic muscle. The potential for either muscle inactivity or exercise to alter mitochondrial dysfunction during cancer cachexia will also be discussed.

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The role of gp130 receptor cytokines in the regulation of metabolic homeostasis

Cited by 45 publications

References 74 publications

Inflammatory Cytokines and BDNF Response to High-Intensity Intermittent Exercise: Effect the Exercise Volume

Inflammatory Cytokines and BDNF Response to High-Intensity Intermittent Exercise: Effect the Exercise Volume

The regulation of skeletal muscle fatigability and mitochondrial function by chronically elevated interleukin‐6

Disrupted Skeletal Muscle Mitochondrial Dynamics, Mitophagy, and Biogenesis during Cancer Cachexia: A Role for Inflammation

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