Diet‐induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration

Brown, Lemuel A.; Lee, D. E.; Patton, Jillian F.; Perry, Richard; Brown, Jacob L.; Baum, Joseph D.; Smith-Blair, Nan; Greene, Nicholas P.; Washington, Tyrone A.

doi:10.1111/apha.12537

Cited by 53 publications

(74 citation statements)

References 43 publications

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“…It is well established that muscle regeneration requires proliferation and differentiation of satellite cells which can be monitored through expression of Myogenin and MyoD (Brown et al, 2015; Marsh, Criswell, Carson, & Booth, 1997; Washington et al, 2011). There was a main effect for injury to increase Myogenin and MyoD mRNA abundance regardless of age (Figures 1A, 1B).…”

Section: Resultsmentioning

confidence: 99%

“…Bupivacaine was administered as previously described (Brown et al, 2015; Washington et al, 2013). Mice were anesthetized with a subcutaneous injection of a cocktail containing ketamine hydrochloride (45 mg/kg body weight), xylazine (3mg/kg body weight), and acepromazine (1 mg/kg body weight).…”

Section: Methodsmentioning

confidence: 99%

“…The Ponceau-stained membranes were digitally scanned. The 45-kDa actin bands were quantified by densitometry and used as a protein loading correction factor for each lane as previously described (Brown et al, 2015; Greene et al, 2014; Washington et al, 2011). …”

Section: Methodsmentioning

confidence: 99%

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Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Perry

Brown

Lee

et al. 2016

Mechanisms of Ageing and Development

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Aging decreases the ability of skeletal muscle to respond to injury. Leucine has been demonstrated to target protein synthetic pathways in skeletal muscle thereby enhancing this response. However, the effect of aging on leucine-induced alterations in protein synthesis at the onset of skeletal muscle regeneration has not been fully elucidated. The purpose of this study was to determine if aging alters skeletal muscle regeneration and leucine-induced alterations in markers of protein synthesis. The tibialis anterior of young (3 months) and aged (24 months) female C57BL/6J mice were injected with either bupivacaine or PBS, and the mice were given ad libitum access to leucine-supplemented or normal drinking water. Protein and gene expression of markers of protein synthesis and degradation, respectively, were analyzed at three days post-injection. Following injury in young mice, leucine supplementation was observed to elevate only p-p70S6K. In aged mice, leucine was shown to elicit higher p-mTOR content with and without injury, and p-4EBP-1 content post-injury. Additionally in aged mice, leucine was shown to elicit higher content of relative p70S6K post-injury. Our study shows that leucine supplementation affects markers of protein synthesis at the onset of skeletal muscle regeneration differentially in young and aged mice.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Perry

Brown

Lee

et al. 2016

Mechanisms of Ageing and Development

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“…A delayed and weakened wound-healing response has already been observed in both obese and diabetic populations. Process that seems to take place because of an impaired inflammatory response within these populations (Pence and Woods 2014; Brown et al 2015; Sinha et al 2017). However, further research in the area is needed to verify this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans

Morales

IglayReger

et al. 2018

Appl. Physiol. Nutr. Metab.

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Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance; however, the role of macrophage infiltration within skeletal muscle is still debatable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative real-time polymerase chain reaction), body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and oral glucose tolerance test) were compared between groups and their associations were analyzed. To validate skeletal muscle findings, we repeated the analyses with macrophage gene expression in adipose tissue. Expression levels of macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in skeletal muscle tissue of obese versus lean participants. Macrophage gene expression was also found to be inversely associated with adiposity, fasting insulin, and HOMA (r = −0.4 ~ −0.6, p < 0.05), as well as positively associated with insulin sensitivity (r = 0.4 ~ 0.8, p < 0.05). On the other hand, adipose tissue macrophage gene expression showed higher levels in obese versus lean participants, presenting a positive association with adiposity levels. Macrophage gene expression, in both skeletal and adipose tissue samples, was only minimally affected by the weight loss intervention. In contrast with the established positive relationship between adiposity and macrophage gene expression, an unexpected inverse correlation between these 2 variables was observed in skeletal muscle tissue. Additionally, muscle macrophage gene expression was inversely correlated with insulin resistance.

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“…Skeletal muscle is unique in its ability to adapt to stress and stimuli (myoplasticity) which is partially dependent on its capacity to signal the repair and restoration of the disrupted or injured cell. The process of myoplasticity involves a group of transcription factors called myogenic regulatory factors (MRFs) which, among other things, signal the activation, direction, and proliferation of satellite cells to restore muscle integrity in response to damage or trauma 27 . This myoplasticity involves satellite cells which lie quiescently in the basal lamina under normal conditions; however, when a muscle fiber becomes damaged or stressed, satellite cells are activated, proliferate, and migrate to the site of injury where they fuse and incorporate themselves into the injury site to help repair the area.…”

Section: Discussionmentioning

confidence: 99%

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

Hydock¹

2017

MLTJ

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SummaryBackground: The skeletal muscle toxicity that accompanies the chemotherapy drug doxorubicin (DOX) may lead to cancer patient weakness and fatigue. This myotoxicity involves myogenic regulatory factor (MRF) disruption which alters muscle integrity and regeneration. Endurance exercise enhances MRF expression and thereby may mitigate DOX-induced MRF disruptions. This study examined the effects of endurance training and DOX treatment on myogenic regulatory factor (MRF) expression. Methods: Male rats were exercise trained (EXER) or remained sedentary (SED) for two weeks. EXER and SED then received either DOX (15 mg/kg) or saline (SAL). Soleus, extensor digitorum longus (EDL), and diaphragm were excised 24 hours post injection, and MRF expression was analyzed. Results: Significant Myf5 drug and activity effects were observed in the soleus with EXER+DOX expressing higher Myf5 than SED+DOX. A significant drug effect was detected in soleus MyoD, and a significant activity effect was detected in soleus Mrf4. No main effects or interactions were observed in the EDL, but in the diaphragm, a significant activity effect was observed for Myf5 with EXER+DOX expressing higher levels than SED+DOX. Conclusion: Doxorubicin treatment increased soleus MRFs and exercise boosted MRF response in soleus and diaphragm suggesting that exercise may enhance regenerative signaling with DOX treatment. Level of evidence: I b, individual randomized controlled trial.

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Diet‐induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration

Abstract: Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.

Cited by 53 publications

References 43 publications

Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

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