Skeletal Muscle In Response Research Articles

Use of NIRS to explore skeletal muscle oxygenation during different training sessions in professional boxing

PurposeThe physiological examination of boxing has been limited to systemic response in amateur athletes. The demands of professional boxing have been overlooked, despite the different competition format. We sought to determine the physiological demands placed on skeletal muscle in professional boxing.MethodsTen male professional boxers (age 26 ± 5 years, height 177 ± 4 cm, weight 71 ± 6 kg) were recruited for this observational study. On different days, the athletes completed 6 × 3 min rounds of pad, bag or spar-based training with 1 min recovery between each round. Prior to each session, participants put on a heart rate monitor and near-infrared spectroscopy attached to the belly of the rectus femoris muscle to record heart rate and muscle oxygenation.ResultsThere were significantly less punches thrown in sparring compared to other training modalities (p < 0.001). Skeletal muscle oxygenation across training modalities consisted of a delay, fast desaturation and steady state. Across rounds there was a significant increase in time delay for desaturation (p = 0.016), rate of fast desaturation (p < 0.001) and duration of fast desaturation (p = 0.019). There was a significant difference in sparring for the heart rate where skeletal muscle oxygenation changes occurred compared to pads or bag sessions (p < 0.001).ConclusionThe findings highlight differences in the skeletal muscle response to the different training modalities. Practitioners need to be aware of the muscular demands of each session to allow optimal adaptation across a training camp. Training needs to allow the skeletal muscle to achieve a new oxygenation steady state rapidly to promote efficient performance across rounds.

Acute exercise in a hot environment increases heat shock protein 70 and peroxisome proliferator-activated receptor γ coactivator 1α mRNA in Thoroughbred horse skeletal muscle.

Heat acclimatization or acclimation training in horses is practiced to reduce physiological strain and improve exercise performance in the heat, which can involve metabolic improvement in skeletal muscle. However, there is limited information concerning the acute signaling responses of equine skeletal muscle after exercise in a hot environment. The purpose of this study was to investigate the hypothesis that exercise in hot conditions induces greater changes in heat shock proteins and mitochondrial-related signaling in equine skeletal muscle compared with exercise in cool conditions. Fifteen trained Thoroughbred horses [4.6 ± 0.4 (mean ± SE) years old; 503 ± 14 kg] were assigned to perform a treadmill exercise test in cool conditions [COOL; Wet Bulb Globe Temperature (WBGT), 12.5°C; n = 8] or hot conditions (HOT; WBGT, 29.5°C; n = 7) consisting of walking at 1.7 m/s for 1 min, trotting at 4 m/s for 5 min, and cantering at 7 m/s for 2 min and at 90% of VO2max for 2 min, followed by walking at 1.7 m/s for 20 min. Heart rate during exercise and plasma lactate concentration immediately after exercise were measured. Biopsy samples were obtained from the middle gluteal muscle before and at 4 h after exercise, and relative quantitative analysis of mRNA expression using real-time RT-PCR was performed. Data were analyzed with using mixed models. There were no significant differences between the two groups in peak heart rate (COOL, 213 ± 3 bpm; HOT, 214 ± 4 bpm; p = 0.782) and plasma lactate concentration (COOL, 13.1 ± 1.4 mmoL/L; HOT, 17.5 ± 1.7 mmoL/L; p = 0.060), while HSP-70 (COOL, 1.9-fold, p = 0.207; HOT, 2.4-fold, p = 0.045), PGC-1α (COOL, 3.8-fold, p = 0.424; HOT, 8.4-fold, p = 0.010), HIF-1α (COOL, 1.6-fold, p = 0.315; HOT, 2.2-fold, p = 0.018) and PDK4 (COOL, 7.6-fold, p = 0.412; HOT, 14.1-fold, p = 0.047) mRNA increased significantly only in HOT at 4 h after exercise. These data indicate that acute exercise in a hot environment facilitates protective response to heat stress (HSP-70), mitochondrial biogenesis (PGC-1α and HIF-1α) and fatty acid oxidation (PDK4).

Transcriptomic Analysis of Human Skeletal Muscle in Response to Aerobic Exercise and Protein Intake.

This study aimed to provide a more comprehensive molecular insight into the effects of aerobic exercise (AE), protein intake (PI), and AE combined with PI on human skeletal muscle by comparing their transcriptomic profiles. Fourteen published datasets obtained from the Gene Expression Omnibus (GEO) database were used. The hub genes were identified in response to acute AE (ACTB, IL6), training AE (UBB, COL1A1), PI (EZH2), acute AE combined with PI (DDIT3), and training AE combined with PI (MYC). Both FOS and MYC were upregulated in response to acute AE, and they were, respectively, downregulated by higher PI and a combination of AE and PI. COL1A1 was upregulated by training AE but was downregulated by higher PI. Results from the gene set enrichment analysis (p < 0.05 and FDR < 25%) showed that AE and PI delivered their impacts on human skeletal muscle in analogous pathways, including aerobic respiration, mitochondrial complexes, extracellular matrix (ECM) remodeling, metabolic process, and immune/inflammatory responses, whereas, PI may attenuate the response of immune/inflammation and ECM remodeling which would be promoted by AE, irrespective of its types. Compared to PI alone, acute AE combined with PI would further promote protein turnover and synthesis, but suppress skeletal muscle contraction and movement.

Acidosis attenuates CPT-I-supported bioenergetics as a potential mechanism limiting lipid oxidation

Fuel interactions in contracting muscle represent a complex interplay between enzymes regulating carbohydrate and fatty acid catabolism, converging in the mitochondrial matrix. While increasing exercise intensity promotes carbohydrate use at the expense of fatty acid oxidation, the mechanisms underlying this effect remain poorly elucidated. As a potential explanation, we investigated whether exercise-induced reductions in intramuscular pH (acidosis) attenuate carnitine palmitoyltransferase-I (CPT-I)-supported bioenergetics, the rate-limiting step for fatty acid oxidation within mitochondria. Specifically, we assessed the effect of a physiologically relevant reduction in pH (pH 7.2 versus 6.8) on single and mixed substrate respiratory responses in murine skeletal muscle isolated mitochondria and permeabilized fibers. While pH did not influence oxidative phosphorylation stoichiometry (ADP/O ratios), coupling efficiency, oxygen affinity, or ADP respiratory responses, acidosis impaired lipid bioenergetics by attenuating respiration with L-carnitine and palmitoyl-CoA, while enhancing the inhibitory effect of malonyl-CoA on CPT-I. These acidotic effects were largely retained following a single bout of intense exercise. At rest, pyruvate and succinate-supported respiration were also impaired by acidosis. However, providing more pyruvate and ADP at pH 6.8 to model increases in glycolytic flux and ATP turnover with intense exercise overcame the acidotic attenuation of carbohydrate-linked oxidative phosphorylation. Importantly, this situation is fundamentally different from lipids where CPT-I substrate sensitivity and availability is impaired at higher power outputs suggesting lipid metabolism may be more susceptible to the effects of acidosis, possibly contributing to fuel shifts with increasing exercise intensity.

Tissue regeneration and gut microbiota-skeletal muscle axis via microRNAs and nutrition: a systematic review

Introduction: In the scenario of muscle regeneration in athletes, maintenance of skeletal muscle function is the prerequisite for tissue homeostasis and increased performance. MicroRNAs play a positive role in expanding our understanding of the controlling factors for skeletal muscle function. Recent progress has been made regarding gut microbiota, regenerative nutrition, and skeletal muscle metabolism. Objective: It was to carry out a systematic review of the main relations of regeneration of skeletal muscle-gut microbiota through nutrological functions, cells, and microRNAs. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from February to April 2023 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 217 articles were found. A total of 97 articles were fully evaluated and 49 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 54 studies at high risk of bias and 34 studies that did not meet the GRADE. It was concluded that miRNAs are widely present in skeletal muscle and play an irreplaceable tuning role in the proliferation, differentiation, apoptosis, development, and other physiological processes of skeletal muscle cells. The proposal that miRNAs are primarily involved in the cell's stress response makes miRNAs ideal for mediating the skeletal muscle response to changes in contractile activity. Research has accumulated evidence that confirms that miRNAs have played an important regulatory role in cell proliferation and differentiation, thus regulating skeletal muscle growth as highlighted in the small intestine by intestinal stem cells (LGR5+). The ketogenic or high-glucose diet regulates the self-renewal balance of LGR5+. Self-renewal and HSC differentiation can be regulated by manipulating vitamin C, A, or D levels and valine restriction. The composition of each athlete's microbiome influences sports performance.

The Role of Physical Exercise in Chronic Kidney Disease

Chronic kidney disease (CKD) affects more than 10% of the general population worldwide, amounting to more than 800 million individuals. Some important conditions associated with CKD are hypertension, diabetes, dyslipidemia, sedentary lifestyle, and smoking. According to World Health Organization (WHO), regular physical activity helps to prevent and manage non-communicable diseases such as diabetes and hypertension, associated with weight reduction. It is known that a decrease in systolic blood pressure is associated with significant reduction in all causes of mortality and major cardiovascular events. As far as diabetes concerned, beyond first-line medication, healthy lifestyle behaviours should be considered, in which physical activity is included. Training leads to improved skeletal muscle response with increased expression and activity of proteins involved in glucose metabolism and insulin sensitivity. Concerning dyslipidemia, one of the recommended interventions encompasses lifestyle, noting that in patients with low, moderate, or high cardiovascular risk, depending on the LDL value, the treatment involves physical activity and weight loss or its association with pharmacotherapy. CKD patients have some particularities that condition the exercise prescription and the interpretation of its benefits. This review is intended to systematize the importance of exercise in CKD and its determinants.

Exercise ameliorates chronic inflammatory response induced by high-fat diet via Sestrin2 in an Nrf2-dependent manner

Chronic inflammation is a major contributor to the development of metabolic disorders and is commonly seen in studies of diet-induced obesity in humans and rodents. Exercise has been shown to have anti-inflammatory properties, though the exact mechanisms are still not fully understood. Sestrins and Nrf2 are of interest to researchers as they are known to protect against inflammation and oxidative stress. In this study, we aim to explore the interconnection between Sestrin2 (SESN2) and Nrf2 and their roles in exercise benefits on chronic inflammation. Our data showed that SESN2 knockout aggravated the abnormalities of body weight, fat mass, and serum lipid that were induced by a high-fat diet (HFD), and a concomitant increase of TNF-α, IL-1β and IL-6 in both serum and skeletal muscle. Notably, exercise was found to reverse these changes, and SESN2 was found to be necessary for exercise to reduce the inflammatory response in skeletal muscles, though not in serum. Immunoprecipitation and bioinformatics prediction experiments further revealed that SESN2 directly binds to Nrf2, indicating a protein-protein interaction between the two. Furthermore, our data demonstrated that SESN2 protein is necessary for exercise-induced effects on Nrf2 pathway in HFD-fed mice, and Nrf2 protein is necessary to enable SESN2 to reduce the inflammation caused by palmitic acid (PA)+ oleic acid (OA) treatment in vitro. Our findings indicate that exercise mitigates chronic inflammation induced by HFD through SESN2 in an Nrf2-dependent manner. Our study reveals a novel molecular mechanism whereby the SESN2/Nrf2 pathway mediates the positive impact of exercise on chronic inflammation.

Nicotine and Microvascular Responses in Skeletal Muscle from Acute Exposure to Cigarettes and Vaping.

Despite claims of safety or harm reduction for electronic cigarettes (E-cig) use (also known as vaping), emerging evidence indicates that E-cigs are not likely safe, or necessarily safer than traditional cigarettes, when considering the user's risk of developing vascular dysfunction/disease. E-cigs are different from regular cigarettes in that E-cig devices are highly customizable, and users can change the e-liquid composition (such as the base solution, flavors, and nicotine level). Since the effects of E-cigs on the microvascular responses in skeletal muscle are poorly understood, we used intravital microscopy with an acute (one-time 10 puff) exposure paradigm to evaluate the individual components of e-liquid on vascular tone and endothelial function in the arterioles of the gluteus maximus muscle of anesthetized C57Bl/6 mice. Consistent with the molecular responses seen with endothelial cells, we found that the peripheral vasoconstriction response was similar between mice exposed to E-cig aerosol or cigarette smoke (i.e., 3R4F reference cigarette); this response was not nicotine dependent, and endothelial cell-mediated vasodilation was not altered within this acute exposure paradigm. We also report that, regardless of the base solution component [i.e., vegetable glycerin (VG)-only or propylene glycol (PG)-only], the vasoconstriction responses were the same in mice with inhalation exposure to 3R4F cigarette smoke or E-cig aerosol. Key findings from this work reveal that some component other than nicotine, in inhaled smoke or aerosol, is responsible for triggering peripheral vasoconstriction in skeletal muscle, and that regardless of one's preference for an E-cig base solution composition (i.e., ratio of VG-to-PG), the acute physiological response to blood vessels appears to be the same. The data suggest that vaping is not likely to be 'safer' than smoking towards blood vessels and can be expected to produce and/or result in the same adverse vascular health outcomes associated with smoking cigarettes.

Cyclin D3 deficiency promotes a slower, more oxidative skeletal muscle phenotype and ameliorates pathophysiology in the mdx mouse model of Duchenne muscular dystrophy.

We previously reported that cyclin D3-null mice display a shift toward the slow, oxidative phenotype in skeletal muscle, improved exercise endurance, and increased energy expenditure. Here, we explored the role of cyclin D3 in the physiologic response of skeletal muscle to external stimuli and in a model of muscle degenerative disease. We show that cyclin D3-null mice exhibit a further transition from glycolytic to oxidative muscle fiber type in response to voluntary exercise and an improved response to fasting. Since fast glycolytic fibers are known to be more susceptible to degeneration in Duchenne muscular dystrophy (DMD), we examined the effects of cyclin D3 inactivation on skeletal muscle phenotype in the mdx mouse model of DMD. Compared with control mdx mice, cyclin D3-deficient mdx mice display a higher proportion of slower and more oxidative myofibers, reduced muscle degenerative/regenerative processes, and reduced myofiber size variability, indicating an attenuation of dystrophic histopathology. Furthermore, mdx muscles lacking cyclin D3 exhibit reduced fatigability during repeated electrical stimulations. Notably, cyclin D3-null mdx mice show enhanced performance during recurrent trials of endurance treadmill exercise, and post-exercise muscle damage results decreased while the regenerative capacity is boosted. In addition, muscles from exercised cyclin D3-deficient mdx mice display increased oxidative capacity and increased mRNA expression of genes involved in the regulation of oxidative metabolism and the response to oxidative stress. Altogether, our findings indicate that depletion of cyclin D3 confers benefits to dystrophic muscle, suggesting that cyclin D3 inhibition may represent a promising therapeutic strategy against DMD.

High-Temperature Stress Induces Autophagy in Rainbow Trout Skeletal Muscle

Ectothermic animals, such as teleosts, have increasingly been exposed to stressful high-temperature events due to global warming. Currently, the effects of thermal stress on skeletal muscle, a key tissue for fish growth, are unknown. This study examined the impact of high-temperature stress on the skeletal muscle transcriptome of rainbow trout (Oncorhynchus mykiss) in control (15 °C) and high-temperature (20 °C) conditions. Additionally, we examined the plasmatic levels of cortisol, glucose, and creatine kinase activity, and examined oxidative damage and autophagy activation in skeletal muscle. High-temperature stress induced significant increases in cortisol and glucose plasmatic levels. Nevertheless, no changes were observed in creatine kinase activity in plasma and skeletal muscle oxidation. Skeletal muscle RNA was isolated and sequenced using the HiSeq Illumina platform. A total of 383,796,290 reads were mapped onto the reference rainbow trout genome. The transcriptomic analysis showed that 293 genes were upregulated in the high-temperature group, mainly associated with autophagosome assembly, amino acid transport, and the glutamine metabolic process. On the other hand, 119 genes were downregulated in the high-temperature group, mainly associated with digestion, proteolysis, and the muscle contraction process. In addition, RT-qPCR of differentially expressed representative genes and Western blot analysis of LC3-II/LC3-I levels confirmed skeletal muscle autophagy induced by high temperature. This study sheds light on intriguing facets of the adaptive response of rainbow trout skeletal muscle to high-temperature stress and provides significant insights into the physiology of autophagy in teleosts.

Determining the Potential Roles of Branched-Chain Amino Acids in the Regulation of Muscle Growth in Common Carp (Cyprinus carpio) Based on Transcriptome and MicroRNA Sequencing.

Branched-chain amino acids (BCAAs) can be critically involved in skeletal muscle growth and body energy homeostasis. Skeletal muscle growth is a complex process; some muscle-specific microRNAs (miRNAs) are involved in the regulation of muscle thickening and muscle mass. Additionally, the regulatory network between miRNA and messenger RNA (mRNA) in the modulation of the role of BCAAs on skeletal muscle growth in fish has not been studied. In this study, common carp was starved for 14 days, followed by a 14-day gavage therapy with BCAAs, to investigate some of the miRNAs and genes that contribute to the regulation of normal growth and maintenance of skeletal muscle in response to short-term BCAA starvation stress. Subsequently, the transcriptome and small RNAome sequencing of carp skeletal muscle were performed. A total of 43,414 known and 1,112 novel genes were identified, in addition to 142 known and 654 novel miRNAs targeting 22,008 and 33,824 targets, respectively. Based on their expression profiles, 2,146 differentially expressed genes (DEGs) and 84 differentially expressed miRNA (DEMs) were evaluated. Kyoto Encyclopedia of Genes and Genome pathways, including the proteasome, phagosome, autophagy in animals, proteasome activator complex, and ubiquitin-dependent protein catabolic process, were enriched for these DEGs and DEMs. Our findings revealed the role of atg5, map1lc3c, ctsl, cdc53, psma6, psme2, myl9, and mylk in skeletal muscle growth, protein synthesis, and catabolic metabolism. Furthermore, miR-135c, miR-192, miR-194, and miR-203a may play key roles in maintaining the normal activities of the organism by regulating genes related to muscle growth, protein synthesis, and catabolism. This study on transcriptome and miRNA reveals the potential molecular mechanisms underlying the regulation of muscle protein deposition and provides new insights into genetic engineering techniques to improve common carp muscle development.

During Resistance Training the Effect of Ibuprofen on Muscle Hypertrophy Regarding Strength and Soreness. A Population Based Cross-Sectional Study

Background: Non-steroidal anti-inflammatory medicines (NSAIDs) are frequently used to speed up post-exercise recovery and lessen discomfort and soreness in muscles. There is a concept that Ibuprofen at high doses has been found to prevent the production of muscle proteins following a session of resistance training. Aims and Objectives: To examine the effects of 400 mg/ day dose of ibuprofen on muscular hypertrophy and strength following resistance exercise. Study Design: This was a population based cross-sectional study. Place and Duration: Present study was conducted in different work out gyms of Lahore region from October 2022 to April 2023. Research Rationale: The combined findings of in vitro and human studies indicate that NSAIDs may blunt the early skeletal muscle responses to exercise. Their widespread use is due to their effectiveness in reducing inflammation, fever, and discomfort. Methodology: Total 100 participants were in this study and all of them provided written informed consent and completed questionnaires about their past training experiences. 70 males and 30 females 20-30 years of age trained their right and left biceps on alternate days 6 sets of 4–10 repetitions, 5 days in week–1, for 8 weeks. All subjects before selection for study completed medical examination blood analysis and health history questionnaires. All participants were received, 400 mg/day of ibuprofen after training their left or right arm. Before and after training muscle thickness of both biceps was measured using ultrasound, and 1 repetition maximum (1 RM) arm curl strength was assessed on both arms. The weights of the dumbbells were chosen so that the required number of repetitions would result in training till failure on each individual set.

Exercise metabolism and adaptation in skeletal muscle.

Viewing metabolism through the lens of exercise biology has proven an accessible and practical strategy to gain new insights into local and systemic metabolic regulation. Recent methodological developments have advanced understanding of the central role of skeletal muscle in many exercise-associated health benefits and have uncovered the molecular underpinnings driving adaptive responses to training regimens. In this Review, we provide a contemporary view of the metabolic flexibility and functional plasticity of skeletal muscle in response to exercise. First, we provide background on the macrostructure and ultrastructure of skeletal muscle fibres, highlighting the current understanding of sarcomeric networks and mitochondrial subpopulations. Next, we discuss acute exercise skeletal muscle metabolism and the signalling, transcriptional and epigenetic regulation of adaptations to exercise training. We address knowledge gaps throughout and propose future directions for the field. This Review contextualizes recent research of skeletal muscle exercise metabolism, framing further advances and translation into practice.

The exercise-mediated metabokine Beta-aminoisobutyric acid is an exercise mimetic driving skeletal muscle metabolic and functional adaptation

Skeletal muscle integrates many of the systemic signals, which contribute to the adaptive remodeling, and beneficial effects of exercise. One mechanism through which muscle mediates the systemic effects of exercise is through muscle-derived hormones known as myokines. We identified the metabolite β-aminoisobutyric acid (BAIBA) as an exercise-mediated small molecule myokine. BAIBA is secreted from muscle in response to increased expression of the transcriptional co-regulator PGC-1α, a master regulator of the muscle adaptive response to exercise. However, how BAIBA functions to regulate the adaptive responses of skeletal muscle to exercise remains poorly understood. We show that BAIBA improves muscle metabolism, exercise efficiency and performance in mice. Oxygen consumption (VO2) and energy expenditure are increased in BAIBA-treated mice. Furthermore, BAIBA increased soleus in situ muscle contractile force, fatigue resistance, mitochondrial number and function. We found that BAIBA drives muscle fiber-type switching to an oxidative phenotype in vivo. BAIBA regulates specific fiber-type gene expression in human myocytes through PPARΔ. Our findings demonstrate that BAIBA is a key paracrine myokine, which, in part, regulates the effects of exercise to improve muscle function with resultant effects on exercise performance. H.N.D. acknowledges the support of the Biotechnology and Biological Sciences Research Council (BB/T004231/1). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 134: A Single-cell Atlas Of Human Skeletal Muscle Tissue In Chronic Limb-threatening Ischemia

Introduction: Chronic limb-threatening ischemia (CLTI) represents end-stage peripheral arterial disease (PAD) and is a significant cause of limb amputation and mortality. Evidence supports the importance of skeletal muscle responses in the pathobiology of CLTI. Skeletal muscle regeneration depends on the coordinated activity of muscle stem cells (MuSCs) and an array of non-myogenic cells, including immune cells and fibroadipogenic progenitors (FAPs). The mechanisms underlying failed muscle regeneration in the CLTI limb are unknown. Single-cell RNA sequencing (scRNA-seq) facilitates the deconvolution of multicellular tissues in homeostatic and pathologic conditions. Herein, we profiled the transcriptomes of 135,203 cells from lower extremity skeletal muscle of PAD patients to construct a cellular atlas of CLTI. Methods: We recruited 12 PAD patients undergoing major limb amputation for CLTI. We obtained proximal (non-ischemic) and distal (ischemic) muscle samples from each patient and used scRNA-seq to profile the transcriptomes of 1,700 – 20,000 cells per sample. Results: We observed 10 distinct cellular populations in the CLTI limb. The predominant cell types were MuSCs, FAPs, and immune cells. There was significant transcriptional heterogeneity in each population; we defined a range of MuSC, FAP, and macrophage sub-populations and identified specific FAPs and macrophages associated with tissue ischemia. Using CellChat analysis, we found differential cell-cell signaling probabilities in ischemic vs. non-ischemic muscle. In ischemic muscle, FAPs are the primary source of outgoing signals, while macrophages are the primary receiver. Conclusions: Our single-cell atlas highlights the transcriptional heterogeneity of cellular responses in the CLTI limb. This atlas will serve as a resource for future studies of the molecular underpinnings of CLTI, advance our understanding of its pathogenesis, and support the development of novel therapies.

Distinct Transcriptional Responses of Skeletal Muscle to Short-Term Cold Exposure in Tibetan Pigs and Bama Pigs.

Piglets are susceptible to cold, and piglet death caused by cold stress leads to economic losses in the pig industry in cold areas. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, but the related mechanism in pigs is unclear. In this study, cold-tolerant Tibetan pigs and cold-sensitive Bama pigs were subjected to either a cold environment (4 °C) or a room temperature environment (25 °C) for 3 days. The biceps femoris (BF) and longissimus dorsi muscle (LDM) were collected for phenotypic analysis, and the BF was used for genome-wide transcriptional profiling. Our results showed that Tibetan pigs had a higher body temperature than Bama pigs upon cold stimulation. RNA-seq data indicated a stronger transcriptional response in the skeletal muscle of Tibetan pigs upon cold stimulation, as more differentially expressed genes (DEGs) were identified with the same criteria (p < 0.05 and fold change > 2). In addition, distinct pathway signaling patterns in skeletal muscle upon cold exposure were found between the breeds of pigs. Mitochondrial beta-oxidation-related genes and pathways were significantly upregulated in Tibetan pigs, indicating that Tibetan pigs may use fatty acids as the primary fuel source to protect against cold. However, the significant upregulation of inflammatory response- and glycolysis-related genes and pathways in the skeletal muscle of Bama pigs suggested that these pigs may use glucose as the primary fuel source in cold environments. Together, our study revealed the distinct transcriptional responses of skeletal muscle to cold stimulation in Tibetan pigs and Bama pigs and provided novel insights for future investigation of the cold adaptation mechanism in pigs.

Exercise Improves the Coordination of the Mitochondrial Unfolded Protein Response and Mitophagy in Aging Skeletal Muscle.

The mitochondrial unfolded protein response (UPRmt) and mitophagy are two mitochondrial quality control (MQC) systems that work at the molecular and organelle levels, respectively, to maintain mitochondrial homeostasis. Under stress conditions, these two processes are simultaneously activated and compensate for each other when one process is insufficient, indicating mechanistic coordination between the UPRmt and mitophagy that is likely controlled by common upstream signals. This review focuses on the molecular signals regulating this coordination and presents evidence showing that this coordination mechanism is impaired during aging and promoted by exercise. Furthermore, the bidirectional regulation of reactive oxygen species (ROS) and AMPK in modulating this mechanism is discussed. The hierarchical surveillance network of MQC can be targeted by exercise-derived ROS to attenuate aging, which offers a molecular basis for potential therapeutic interventions for sarcopenia.

Decreased insulin-like growth factor-1 expression in response to mechanical loading is associated with skeletal muscle anabolic resistance in cancer cachexia

ObjectiveCachexia is a systemic metabolic syndrome characterized by loss of body weight and skeletal muscle mass during chronic wasting diseases, such as cancer. Skeletal muscle in cancer cachexia is less responsive to anabolic factors including mechanical loading; however, the precise molecular mechanism is largely unknown. In this study, we examined the underlying mechanism of anabolic resistance in skeletal muscle in a cancer cachexia model. MethodsCD2F1 mice (male, 8 weeks old) were subcutaneously transplanted (1 × 106 cells per mouse) with a mouse colon cancer-derived cell line (C26) as a model of cancer cachexia. Mechanical overload of the plantaris muscle by synergist tenotomy was performed during the 2nd week and the plantaris muscle was sampled at the 4th week following C26 transplantation. ResultsThe hypertrophic response of skeletal muscle (increased skeletal muscle weight/protein synthesis efficiency and activation of mechanistic target of rapamycin complex 1 signaling) associated with mechanical overload was significantly suppressed during cancer cachexia. Screening of gene expression profile and pathway analysis using microarray revealed that blunted muscle protein synthesis was associated with cancer cachexia and was likely induced by downregulation of insulin-like growth factor-1 (IGF-1) and impaired activation of IGF-1-dependent signaling. ConclusionsThese observations indicate that cancer cachexia induces resistance to muscle protein synthesis, which may be a factor for inhibiting the anabolic adaptation of skeletal muscle to physical exercise in cancer patients.

Mass spectrometry-based proteomics approaches to interrogate skeletal muscle adaptations to exercise.

Acute exercise and chronic exercise training elicit beneficial whole-body changes in physiology that ultimately depend on profound alterations to the dynamics of tissue-specific proteins. Since the work accomplished during exercise owes predominantly to skeletal muscle, it has received the majority of interest from exercise scientists that attempt to unravel adaptive mechanisms accounting for salutary metabolic effects and performance improvements that arise from training. Contemporary scientists are also beginning to use mass spectrometry-based proteomics, which is emerging as a powerful approach to interrogate the muscle protein signature in a more comprehensive manner. Collectively, these technologies facilitate the analysis of skeletal muscle protein dynamics from several viewpoints, including changes to intracellular proteins (expression proteomics), secreted proteins (secretomics), post-translational modifications as well as fiber-, cell-, and organelle-specific changes. This review aims to highlight recent literature that has leveraged new workflows and advances in mass spectrometry-based proteomics to further our understanding of training-related changes in skeletal muscle. We call attention to untapped areas in skeletal muscle proteomics research relating to exercise training and metabolism, as well as basic points of contention when applying mass spectrometry-based analyses, particularly in the study of human biology. We further encourage researchers to couple the hypothesis-generating and descriptive nature of omics data with functional analyses that propel our understanding of the complex adaptive responses in skeletal muscle that occur with acute and chronic exercise.

Different Resistance Exercise Loading Paradigms Similarly Affect Skeletal Muscle Gene Expression Patterns of Myostatin-Related Targets and mTORC1 Signaling Markers.

Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise.