Effects of Aerobic Exercise on the Regulation of Inflammation-Related Gene Expression in the Skeletal Muscle of Ovariectomized Obese Mice: Improvement of Skeletal Muscle Inflammation by Swimming Exercise

Skeletal muscle inflammation and atrophy are closely associated with metabolic impairment such as insulin resistance. Quercetin, a natural polyphenol flavonoid, is known to elicit anti-inflammatory and antioxidant activities. In this study, we investigated its effect on obesity-induced skeletal muscle inflammation and atrophy in mice. Male C57BL/6 mice were fed a regular diet, a high-fat diet (HFD), and an HFD supplemented with quercetin for nine weeks. Quercetin reduced levels of inflammatory cytokines and macrophage accumulation in the skeletal muscle of the HFD-fed obese mice. It also reduced transcript and protein levels of the specific atrophic factors, Atrogin-1 and MuRF1, in the skeletal muscle of the HFD-fed obese mice, and protected against the reduction of muscle mass and muscle fiber size. In vitro, quercetin markedly diminished transcript levels of inflammatory receptors and activation of their signaling molecules (ERK, p38 MAPK, and NF-κB) in cocultured myotubes/macrophages, and this was accompanied by reduced expression of the atrophic factors. Together, these findings suggest that quercetin reduces obesity-induced skeletal muscle atrophy by inhibiting inflammatory receptors and their signaling pathway. Quercetin may be useful for preventing obesity-induced muscle inflammation and sarcopenia.

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REDD1 induction regulates the skeletal muscle gene expression signature following acute aerobic exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00120.2017 ◽

2017 ◽

Vol 313 (6) ◽

pp. E737-E747 ◽

Cited By ~ 9

Author(s):

Bradley S. Gordon ◽

Jennifer L. Steiner ◽

Michael L. Rossetti ◽

Shuxi Qiao ◽

Leif W. Ellisen ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Aerobic Exercise ◽

Acute Exercise ◽

Gene Expression Signature ◽

Model Systems ◽

Expression Signature ◽

Altered Gene Expression ◽

Altered Gene ◽

Exercise Induced

The metabolic stress placed on skeletal muscle by aerobic exercise promotes acute and long-term health benefits in part through changes in gene expression. However, the transducers that mediate altered gene expression signatures have not been completely elucidated. Regulated in development and DNA damage 1 (REDD1) is a stress-induced protein whose expression is transiently increased in skeletal muscle following acute aerobic exercise. However, the role of this induction remains unclear. Because REDD1 altered gene expression in other model systems, we sought to determine whether REDD1 induction following acute exercise altered the gene expression signature in muscle. To do this, wild-type and REDD1-null mice were randomized to remain sedentary or undergo a bout of acute treadmill exercise. Exercised mice recovered for 1, 3, or 6 h before euthanization. Acute exercise induced a transient increase in REDD1 protein expression within the plantaris only at 1 h postexercise, and the induction occurred in both cytosolic and nuclear fractions. At this time point, global changes in gene expression were surveyed using microarray. REDD1 induction was required for the exercise-induced change in expression of 24 genes. Validation by RT-PCR confirmed that the exercise-mediated changes in genes related to exercise capacity, muscle protein metabolism, neuromuscular junction remodeling, and Metformin action were negated in REDD1-null mice. Finally, the exercise-mediated induction of REDD1 was partially dependent upon glucocorticoid receptor activation. In all, these data show that REDD1 induction regulates the exercise-mediated change in a distinct set of genes within skeletal muscle.

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Nutritional regulation of renal lipogenic factor expression in mice: comparison to regulation in the liver and skeletal muscle

AJP Renal Physiology ◽

10.1152/ajprenal.00594.2016 ◽

2017 ◽

Vol 313 (4) ◽

pp. F887-F898 ◽

Cited By ~ 2

Author(s):

Suk-Jeong Kim ◽

Ji-Eun Kim ◽

Yong-Woon Kim ◽

Jong-Yeon Kim ◽

So-Young Park

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Nutritional Regulation ◽

Obese Mice ◽

Lipogenic Gene ◽

Protein Levels ◽

Lipogenic Gene Expression ◽

Element Binding Protein ◽

Fasting And Refeeding ◽

Renal Expression

Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 h and restored by refeeding, whereas the mRNA levels of forkhead box O (FOXO)1/3 were increased by fasting and restored by refeeding. Accordingly, protein levels of SREBP-1, FAS, and phosphorylated FOXO1/3 were reduced by fasting and restored by refeeding. The patterns of lipogenic factors expression in the kidney were similar to those in the liver and skeletal muscle. However, this phasic regulation of renal lipogenic gene expression was blunted in diet-induced obese mice. LXR agonist TO901317 increased the lipogenic gene expression and the protein levels of SREBP-1 precursor and FAS but not nuclear SREBP-1. Moreover, increases in insulin-induced gene mRNA and nuclear carbohydrate-responsive element binding protein (ChREBP) levels were observed in the TO901317-treated mice. These results suggest that the kidney shows flexible suppression and restoration of lipogenic factors following fasting and refeeding in lean mice, but this is blunted in obese mice. LXR is involved in the renal expression of lipogenic enzymes, and ChREBP may mediate the response.

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Altered Body Composition and Muscle Anabolic, Catabolic and Metabolic Gene Expression in COPD Patients with Elevated Skeletal Muscle Inflammation.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a4200 ◽

2009 ◽

Author(s):

HR Gosker ◽

AH Remels ◽

P Sliwinski ◽

M Polkey ◽

J Galdiz ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Body Composition ◽

Muscle Inflammation ◽

Metabolic Gene ◽

Copd Patients ◽

Metabolic Gene Expression

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Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation in women

Journal of Applied Physiology ◽

10.1152/japplphysiol.00655.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1493-1504

Author(s):

Kaleen M. Lavin ◽

Ryan K. Perkins ◽

Bozena Jemiolo ◽

Ulrika Raue ◽

Scott W. Trappe ◽

...

Keyword(s):

Skeletal Muscle ◽

Aerobic Exercise ◽

Muscle Inflammation ◽

Age Related ◽

Aging Men ◽

Anti Inflammatory ◽

Exercise Induced ◽

Effects Of Aging ◽

Positive Effect ◽

Lifelong Exercise

We previously reported a positive effect of lifelong exercise on skeletal muscle inflammation in aging men. This parallel investigation in women revealed that lifelong exercise did not protect against age-related increases in circulating or muscle inflammation and that preparedness to handle loading stress was not preserved by lifelong exercise. Further investigation is necessary to understand why lifelong aerobic exercise may not confer the same anti-inflammatory benefits in women as it does in men.

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Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice

Scientific Reports ◽

10.1038/s41598-019-56922-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Carla Igual Gil ◽

Mario Ost ◽

Juliane Kasch ◽

Sara Schumann ◽

Sarah Heider ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Acute Exercise ◽

Treadmill Running ◽

Exercise Stress ◽

Metabolic Phenotype ◽

Obese Mice ◽

Active Lifestyle ◽

Post Exercise ◽

Stress Markers

AbstractPhysical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57Bl/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.

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