<scp>PGC</scp>‐1<i>α</i>4 gene expression is suppressed by the <scp>IL</scp>‐6—<scp>MEK</scp>—<scp>ERK</scp> 1/2 <scp>MAPK</scp> signalling axis and altered by resistance exercise, obesity and muscle injury

Brown, Jacob L.; Rosa‐Caldwell, Megan E.; Lee, David E.; Brown, Lemuel A.; Perry, Richard; Shimkus, Kevin L.; Blackwell, Thomas A.; Fluckey, James D.; Carson, James A.; Dridi, Sami; Washington, Tyrone A.

doi:10.1111/apha.12826

Cited by 27 publications

(32 citation statements)

References 46 publications

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“…There are several PGC-1 isoforms, and each has significant but independent roles in oxidative metabolism. PGC-1 α 4 regulates muscle protein synthesis through IGF-1 and myostatin signaling cascades [133, 134]. PGC-1 β can regulate myosin heavy-chain isoform expression, and increased expression induces an oxidative muscle phenotype [135].…”

Section: Mitochondrial Dysfunction In Cachectic Muscle and Inflammmentioning

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

137

167

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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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Section: Mitochondrial Dysfunction In Cachectic Muscle and Inflammmentioning

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

137

167

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“…In the manuscript by Brown et al . (), it was initially discovered that global deletion of IL‐6 in mice increased PGC‐1 α 4 expression in the skeletal muscle nearly sevenfold, supporting a link between IL‐6 expression/signalling and the expression of this splice variant. Further mechanistic work in C 2 C 12 myotubes showed that exogenous IL‐6 administration effectively decreased PGC‐1 α 4 expression through a MEK/ERK sensitive mechanism.…”

mentioning

confidence: 97%

“…, Brown et al . ). Alternatively, the transient MEK/ERK activation following resistance exercise may be a different stimulus compared to the more chronic activation that appears to occur with ageing (Brown et al .…”

mentioning

confidence: 97%

“…Alternatively, the transient MEK/ERK activation following resistance exercise may be a different stimulus compared to the more chronic activation that appears to occur with ageing (Brown et al . ). Therefore, it is possible that the changes in PGC‐1 α 4 expression following MEK/ERK activation may be linked to the transient vs. chronic activation.…”

mentioning

confidence: 97%

“…In the current issue of Acta Physiologica , Brown et al . () describes a novel regulatory mechanism for the expression of the peroxisome proliferator‐activated receptor gamma co‐activator 1 alpha (PGC‐1 α ) splice variant 4 (PGC‐1 α 4). Since its discovery, the parent PGC‐1 α gene has been at the forefront of muscle biology research as it significantly altered muscle phenotype in both pathological and physiological model systems (Lin et al .…”

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confidence: 99%

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A novel and complex mechanism regulating PGC‐1α4 expression

Gordon

2017

Acta Physiologica

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Resistance training restores metabolic alterations induced by monosodium glutamate in a sex‐dependent manner in male and female rats

Quines

Jardim

Araujo

et al. 2019

J of Cellular Biochemistry

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Despite resistance exercises being associated with health outcomes, numerous issues are still unresolved and further research is required before the exercise can faithfully be prescribed as medicine. The goal of this study was to investigate whether there are sex differences in resistance training effects on metabolic alterations induced by monosodium glutamate (MSG), a model of obesity, in male and female rats. Male and female Wistar rats received MSG (4 g/kg body weight/day, s.c.) from postnatal day 1 to 10. After 10 days from MSG administration, the rats were separated into two groups: MSG-sedentary and MSG-exercised. At postnatal day 60, the animals started a resistance training protocol in an 80 degrees inclined vertical ladder apparatus and performed it for 7 weeks. Control rats received saline solution and were divided in saline-sedentary and saline-exercised. Resistance training restored all plasma biochemical parameters (glucose, cholesterol, triglycerides, aspartate aminotransferase, and alanine aminotransferase) increased in male and female rats treated with MSG. The MSG administration induced hyperglycemia associated with a decrease in the skeletal muscle glucose transporter 4 (GLUT4) levels and accompanied by deregulation in proteins, G-6Pase, and tyrosine aminotransferase, involved in hepatic glucose metabolism of male and female rats. MSG induced dyslipidemia and lipotoxicity in the liver and skeletal muscle of male rats. Regarding female rats, lipotoxicity was found only in the skeletal muscle.The resistance training had beneficial effects against metabolic alterations induced by MSG in male and female rats, through regulation of proteins (GLUT2, protein kinase B, and GLUT4) involved in glucose and lipid pathways in the liver and skeletal muscle. K E Y W O R D S glucose metabolism, lipotoxicity, monosodium glutamate (MSG), resistance exercise, sex J Cell Biochem. 2019;120:13426-13440. wileyonlinelibrary.com/journal/jcb 13426 |

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PGC‐1α4 gene expression is suppressed by the IL‐6—MEK—ERK 1/2 MAPK signalling axis and altered by resistance exercise, obesity and muscle injury

Abstract: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.

Cited by 27 publications

References 46 publications

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

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

A novel and complex mechanism regulating PGC‐1α4 expression

Resistance training restores metabolic alterations induced by monosodium glutamate in a sex‐dependent manner in male and female rats

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