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Sample records for regulating muscle mass

  1. TAK1 regulates skeletal muscle mass and mitochondrial function

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    Hindi, Sajedah M.; Sato, Shuichi; Xiong, Guangyan; Bohnert, Kyle R.; Gibb, Andrew A.; Gallot, Yann S.; McMillan, Joseph D.; Hill, Bradford G.

    2018-01-01

    Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-β–activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. In addition, targeted inactivation of TAK1 leads to the accumulation of dysfunctional mitochondria and oxidative stress in skeletal muscle of adult mice. Inhibition of TAK1 does not attenuate denervation-induced muscle wasting in adult mice. Finally, TAK1 activity is highly upregulated during overload-induced skeletal muscle growth, and inactivation of TAK1 prevents myofiber hypertrophy in response to functional overload. Overall, our study demonstrates that TAK1 is a key regulator of skeletal muscle mass and oxidative metabolism. PMID:29415881

  2. Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

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    Davey, Jonathan R.; Watt, Kevin I.; Parker, Benjamin L.; Chaudhuri, Rima; Ryall, James G.; Cunningham, Louise; Qian, Hongwei; Sartorelli, Vittorio; Chamberlain, Jeffrey; James, David E.

    2016-01-01

    The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID:27182554

  3. Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3.

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    Ligen Lin

    Full Text Available We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3. Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER, indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.

  4. The Regulation of Muscle Mass by Endogenous Glucocorticoids

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    Daniel L Marks

    2015-02-01

    Full Text Available Glucocorticoids are highly conserved fundamental regulators of energy homeostasis. In response to stress in the form of perceived danger or acute inflammation, glucocorticoids are released from the adrenal gland, rapidly mobilizing energy from carbohydrate, fat and protein stores. In the case of inflammation, mobilized protein is critical for the rapid synthesis of acute phase reactants and an efficient immune response to infection. While adaptive in response to infection, chronic mobilization can lead to a p rofound depletion of energy stores. Skeletal muscle represents the major body store of protein, and can become substantially atrophied under conditions of chronic inflammation. Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. Protein synthesis is also suppressed at the level of translational initiation, preventing the production of new myofibrillar protein. Glucocorticoids also antagonize the action of anabolic regulators such as insulin further exacerbating the loss of protein and muscle mass. The loss of muscle mass in the context of chronic disease is a key feature of cachexia and contributes substantially to morbidity and mortality. A growing body of evidence demonstrates that glucocorticoid signaling is a common mediator of wasting, irrespective of the underlying initiator or disease state. This review will highlight fundamental mechanisms of glucocorticoid signaling and detail the mechanisms of glucocorticoid-induced muscle atrophy. Additionally, the evidence for glucocorticoids as a driver of muscle wasting in numerous disease states will be discussed. Given the burden of wasting diseases and the nodal nature of glucocorticoid signaling, effective anti-glucocorticoid therapy would be a valuable clinical tool. Therefore, the progress and potential pitfalls in the development of glucocorticoid antagonists for muscle wasting will

  5. The Intriguing Regulators of Muscle Mass in Sarcopenia and Muscular Dystrophy

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    Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

    2014-01-01

    Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This revie...

  6. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

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    Mee-Sup Yoon

    2017-10-01

    Full Text Available Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

  7. Immobilization/remobilization and the regulation of muscle mass

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    Almon, R. R.

    1983-01-01

    The relationship between animal body weight and the wet and dry weights of the soleus and EDL muscles was derived. Procedures were examined for tissue homogenization, fractionation, protein determination and DNA determination. A sequence of procedures and buffers were developed to carry out all analyses on one small muscle. This would yield a considerable increase in analytical strength associated with paired statistics. The proposed casting procedure which was to be used for immobilization was reexamined.

  8. Alterations in molecular muscle mass regulators after 8 days immobilizing Special Forces mission

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    Jespersen, J. G.; Mikkelsen, Ulla Ramer; Nedergaard, A.

    2015-01-01

    In military operations, declined physical capacity can endanger the life of soldiers. During special support and reconnaissance (SSR) missions, Special Forces soldiers sustain 1-2 weeks full-body horizontal immobilization, which impairs muscle strength and performance. Adequate muscle mass and st...

  9. The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice

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    You, Jae-Sung; Anderson, Garrett B.; Dooley, Matthew S.; Hornberger, Troy A.

    2015-01-01

    ABSTRACT The maintenance of skeletal muscle mass contributes substantially to health and to issues associated with the quality of life. It has been well recognized that skeletal muscle mass is regulated by mechanically induced changes in protein synthesis, and that signaling by mTOR is necessary for an increase in protein synthesis and the hypertrophy that occurs in response to increased mechanical loading. However, the role of mTOR signaling in the regulation of protein synthesis and muscle mass during decreased mechanical loading remains largely undefined. In order to define the role of mTOR signaling, we employed a mouse model of hindlimb immobilization along with pharmacological, mechanical and genetic means to modulate mTOR signaling. The results first showed that immobilization induced a decrease in the global rates of protein synthesis and muscle mass. Interestingly, immobilization also induced an increase in mTOR signaling, eIF4F complex formation and cap-dependent translation. Blocking mTOR signaling during immobilization with rapamycin not only impaired the increase in eIF4F complex formation, but also augmented the decreases in global protein synthesis and muscle mass. On the other hand, stimulating immobilized muscles with isometric contractions enhanced mTOR signaling and rescued the immobilization-induced decrease in global protein synthesis through a rapamycin-sensitive mechanism that was independent of ribosome biogenesis. Unexpectedly, the effects of isometric contractions were also independent of eIF4F complex formation. Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR signaling, cap-dependent translation and global protein synthesis, and prevented the reduction in fiber size. Therefore, we conclude that the activation of mTOR signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization. Furthermore, these results indicate

  10. Molecular regulation of high muscle mass in developing Blonde d'Aquitaine cattle foetuses

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    Isabelle Cassar-Malek

    2017-10-01

    Full Text Available The Blonde d'Aquitaine (BA is a French cattle breed with enhanced muscularity, partly attributable to a MSTN mutation. The BA m. Semitendinosus has a faster muscle fibre isoform phenotype comprising a higher proportion of fast type IIX fibres compared to age-matched Charolais (CH. To better understand the molecular network of modifications in BA compared to CH muscle, we assayed the transcriptomes of the m. Semitendinosus at 110, 180, 210 and 260 days postconception (dpc. We used a combination of differential expression (DE and regulatory impact factors (RIF to compare and contrast muscle gene expression between the breeds. Prominently developmentally regulated genes in both breeds reflected the replacement of embryonic myosin isoforms (MYL4, MYH3 with adult isoforms (MYH1 and the upregulation of mitochondrial metabolism (CKMT2, AGXT2L1 in preparation for birth. However, the transition to a fast, glycolytic muscle phenotype in the MSTN mutant BA is detectable through downregulation of various slow twitch subunits (TNNC1, MYH7, TPM3, CSRP3 beyond 210 dpc, and a small but consistent genome-wide reduction in mRNA encoding the mitoproteome. Across the breeds, NRIP2 is the regulatory gene possessing a network change most similar to that of MSTN.

  11. Purification and Crystallization of Murine Myostatin: A Negative Regulator of Muscle Mass

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    Hong, Young S.; Adamek, Daniel; Bridge, Kristi; Malone, Christine C.; Young, Ronald B.; Miller, Teresa; Karr, Laurel

    2004-01-01

    Myostatin (MSTN) has been crystallized and its preliminary X-ray diffraction data were collected. MSTN is a negative regulator of muscle growt/differentiation and suppressor of fat accumulation. It is a member of TGF-b family of proteins. Like other members of this family, the regulation of MSTN is critically tied to its process of maturation. This process involves the formation of a homodimer followed by two proteolytic steps. The first proteolytic cleavage produces a species where the n-terminal portion of the dimer is covalently separated from, but remains non-covalently bound to, the c-terminal, functional, portion of the protein. The protein is activated upon removal of the n-terminal "pro-segment" by a second n-terminal proteolytic cut by BMP-1 in vivo, or by acid treatment in vitro. Understanding the structural nature and physical interactions involved in these regulatory processes is the objective of our studies. Murine MSTN was purified from culture media of genetically engineered Chinese Hamster Ovary cells by multicolumn purification process and crystallized using the vapor diffusion method.

  12. Signalling pathways regulating muscle mass in ageing skeletal muscle. The role of the IGF1-Akt-mTOR-FoxO pathway

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    Sandri, M.; Barberi, L.; Bijlsma, A.Y.; Blaauw, B.; Dyar, K.A.; Milan, G.; Mammucari, C.; Meskers, C.G.M.; Pallafacchina, G.; Paoli, A.; Pion, D.; Roceri, M.; Romanello, V.; Serrano, A.L.; Toniolo, L.; Larsson, L.; Maier, A.B.; Munoz-Canoves, P.; Musaro, A.; Pende, M.; Reggiani, C.; Rizzuto, R.; Schiaffino, S.

    2013-01-01

    During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions

  13. Nutritional interventions to preserve skeletal muscle mass

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    Backx, Evelien M.P.

    2016-01-01

    Muscle mass is the main predictor for muscle strength and physical function. The amount of muscle mass can decline rapidly during periods of reduced physical activity or during periods of energy intake restriction. For athletes, it is important to maintain muscle mass, since the loss of muscle is

  14. Muscle Mass and Weight Gain Nutritional Supplements

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    Campbell, Bill

    There are numerous sports supplements available that claim to increase lean body mass. However, for these sports supplements to exert any favorable changes in lean body mass, they must influence those factors regulating skeletal muscle hypertrophy (i.e., satellite cell activity, gene transcription, protein translation). If a given sports supplement does favorably influence one of these regulatory factors, the result is a positive net protein balance (in which protein synthesis exceeds protein breakdown). Sports supplement categories aimed at eliciting a positive net protein balance include anabolic hormone enhancers, nutrient timing pre- and postexercise workout supplements, anticatabolic supplements, and nitric oxide boosters. Of all the sports supplements available, only a few have been subject to multiple clinical trials with repeated favorable outcomes relative to increasing lean body mass. This chapter focuses on these supplements and others that have a sound theoretical rationale in relation to increasing lean body mass.

  15. Low Muscle Mass and Breast Cancer Survival

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    In a new study, researchers compared the risk of death for women with breast cancer who had low skeletal muscle mass, or sarcopenia, at diagnosis and women who had adequate muscle mass. Learn what they found and what it might mean for patients in this Cancer Currents blog post.

  16. Calcium regulation and muscle disease.

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    Gommans, I.M.P.; Vlak, M.; Haan, A. de; Engelen, B.G.M. van

    2002-01-01

    Changes in intracellular Ca2+-concentration play an important role in the excitation-contraction-relaxation cycle of skeletal muscle. In this review we describe various inheritable muscle diseases to highlight the role of Ca2+-regulatory mechanisms. Upon excitation the ryanodine receptor releases

  17. The Emerging Role of Skeletal Muscle Metabolism as a Biological Target and Cellular Regulator of Cancer-Induced Muscle Wasting

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    Carson, James A.; Hardee, Justin P.; VanderVeen, Brandon N.

    2015-01-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle’s metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function regulation, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

  18. Muscle strength rather than muscle mass is associated with osteoporosis in older Chinese adults

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    Yixuan Ma

    2018-02-01

    Conclusion: Based on our study, muscle strength rather than muscle mass is negatively associated with OS in older people; thus, we should pay more attention to muscle strength training in the early stage of the OS.

  19. Supplemental protein in support of muscle mass and health: advantage whey.

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    Devries, Michaela C; Phillips, Stuart M

    2015-03-01

    Skeletal muscle is an integral body tissue playing key roles in strength, performance, physical function, and metabolic regulation. It is essential for athletes to ensure that they have optimal amounts of muscle mass to ensure peak performance in their given sport. However, the role of maintaining muscle mass during weight loss and as we age is an emerging concept, having implications in chronic disease prevention, functional capacity, and quality of life. Higher-protein diets have been shown to: (1) promote gains in muscle mass, especially when paired with resistance training; (2) spare muscle mass loss during caloric restriction; and (3) attenuate the natural loss of muscle mass that accompanies aging. Protein quality is important to the gain and maintenance of muscle mass. Protein quality is a function of protein digestibility, amino acid content, and the resulting amino acid availability to support metabolic function. Whey protein is one of the highest-quality proteins given its amino acid content (high essential, branched-chain, and leucine amino acid content) and rapid digestibility. Consumption of whey protein has a robust ability to stimulate muscle protein synthesis. In fact, whey protein has been found to stimulate muscle protein synthesis to a greater degree than other proteins such as casein and soy. This review examines the existing data supporting the role for protein consumption, with an emphasis on whey protein, in the regulation of muscle mass and body composition in response to resistance training, caloric restriction, and aging. © 2015 Institute of Food Technologists®

  20. Gravity and body mass regulation

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    Warren, L. E.; Horwitz, B. A.; Fuller, C. A.

    1997-01-01

    The effects of altered gravity on body mass, food intake, energy expenditure, and body composition are examined. Metabolic adjustments are reviewed in maintenance of energy balance, neural regulation, and humoral regulation are discussed. Experiments with rats indicate that genetically obese rats respond differently to hypergravity than lean rats.

  1. Muscle metaboreflex and autonomic regulation of heart rate in humans

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    Fisher, James P; Adlan, Ahmed M; Shantsila, Alena

    2013-01-01

    ) conditions, but attenuated with β-adrenergic blockade (0.2 ± 1 beats min(-1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg......We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling...... exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β1-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR...

  2. Muscle Strength and Muscle Mass in Older Patients during Hospitalization: The EMPOWER Study

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    Van Ancum, Jeanine M.; Scheerman, Kira; Pierik, Vincent D.; Numans, Siger T.; Verlaan, Sjors; Smeenk, Hanne E.; Slee-Valentijn, Monique; Kruizinga, Roeliene C.; Meskers, Carel G.M.; Maier, Andrea B.

    2017-01-01

    Background Low muscle strength and muscle mass are associated with an increased length of hospital stay and higher mortality rate in inpatients. To what extent hospitalization affects muscle strength and muscle mass is unclear. Objective We aimed to assess muscle strength and muscle mass at admission and during hospitalization in older patients and its relation with being at risk of geriatric conditions. Methods The EMPOWER study included patients aged 70 years and older, admitted to 4 wards of the VU University Medical Center in the Netherlands between April and December 2015. At admission, patients were screened for being at risk of 4 geriatric conditions: delirium, falls, malnutrition, and functional disability. At admission and at discharge, muscle strength and muscle mass were assessed. Results A total of 373 patients (mean age, standard deviation [SD]: 79.6, 6.38 years) were included at admission, and 224 patients (mean age, SD: 80.1, 6.32 years) at discharge. At admission, lower muscle strength in both female and male patients and low muscle mass in male patients were associated with being at risk of a higher cumulative number of geriatric conditions. Muscle strength increased during hospitalization, but no change in muscle mass was observed. Changes in muscle measures were not associated with being at risk of geriatric conditions. Discussion Older patients with lower muscle strength and muscle mass at admission were at risk of a higher cumulative number of geriatric conditions. However, being at risk of geriatric conditions did not forecast further decrease in muscle strength and muscle mass during hospitalization PMID:28817825

  3. Myostatin genotype regulates muscle-specific miRNA expression in mouse pectoralis muscle

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    Cheng Ye

    2010-11-01

    Full Text Available Abstract Background Loss of functional Myostatin results in a dramatic increase in skeletal muscle mass. It is unknown what role miRNAs play in Myostatin mediated repression of skeletal muscle mass. We hypothesized that Myostatin genotype would be associated with the differential expression of miRNAs in skeletal muscle. Findings Loss of functional Myostatin resulted in a significant increase (p .2 on miR-24 expression level. Myostatin genotype did not affect the expression level of MyoD or Myogenin (P > 0.5. Conclusions Myostatin may regulates the expression of miRNAs such as miR-133a, miR-133b, miR-1, and miR-206 in skeletal muscle as it has been observed that the expression of those miRNAs are significantly higher in myostatin null mice compared to wild type and heterozygous mice. In contrast, expression of myogenic factors such as MyoD or Myogenin has not been affected by myostatin in the muscle tissue.

  4. Androgens regulate gene expression in avian skeletal muscles.

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    Matthew J Fuxjager

    Full Text Available Circulating androgens in adult reproductively active male vertebrates influence a diversity of organ systems and thus are considered costly. Recently, we obtained evidence that androgen receptors (AR are expressed in several skeletal muscles of three passeriform birds, the golden-collared manakin (Manacus vitellinus, zebra finch (Taenopygia guttata, and ochre-bellied flycatcher (Mionectes oleagieus. Because skeletal muscles that control wing movement make up the bulk of a bird's body mass, evidence for widespread effects of androgen action on these muscles would greatly expand the functional impact of androgens beyond their well-characterized effects on relatively discrete targets throughout the avian body. To investigate this issue, we use quantitative PCR (qPCR to determine if androgens alter gene mRNA expression patterns in wing musculature of wild golden-collared manakins and captive zebra finches. In manakins, the androgen testosterone (T up-regulated expression of parvalbumin (PV and insulin-like growth factor I (IGF-I, two genes whose products enhance cellular Ca(2+ cycling and hypertrophy of skeletal muscle fibers. In T-treated zebra finches, the anti-androgen flutamide blunted PV and IGF-I expression. These results suggest that certain transcriptional effects of androgen action via AR are conserved in passerine skeletal muscle tissue. When we examined wing muscles of manakins, zebra finches and ochre-bellied flycatchers, we found that expression of PV and IGF-I varied across species and in a manner consistent with a function for AR-dependent gene regulation. Together, these findings imply that androgens have the potential to act on avian muscle in a way that may enhance the physicality required for successful reproduction.

  5. CORRELATIONS BETWEEN MUSCLE MASS, MUSCLE STRENGTH, PHYSICAL PERFORMANCE, AND MUSCLE FATIGUE RESISTANCE IN COMMUNITY-DWELLING ELDERLY SUBJECTS

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    Elizabeth

    2016-03-01

    Full Text Available Objective: To determine the correlations between muscle mass, muscle strength, physical performance, and muscle fatigue resistance in community-dwelling elderly people in order to elucidate factors which contribute to elderly’s performance of daily activities. Methods: A cross-sectional study was conducted on community-dwelling elderly in Bandung from September to December 2014. One hundred and thirty elderly, 60 years old or above, were evaluated using bioelectrical impedance analysis to measure muscle mass; grip strength to measure muscle strength and muscle fatigue resistance; habitual gait speed to measure physical performance; and Global Physical Activity Questionnaire (GPAQ to assess physical activity. Results: There were significant positive correlations between muscle mass (r=0,27, p=0,0019, muscle strength (r=0,26, p=0,0024, and physical performance (r=0,32, p=0,0002 with muscle fatigue resistance. Physical performance has the highest correlation based on multiple regression test (p=0,0025. In association with muscle mass, the physical activity showed a significant positive correlation (r=0,42, p=0,0000. Sarcopenia was identified in 19 (14.61% of 130 subjects. Conclusions: It is suggested that muscle mass, muscle strength, and physical performance influence muscle fatigue resistance.

  6. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

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    Brown, Laura D.

    2014-01-01

    Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present for the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts development of muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or “catch up” postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts towards improving muscle growth early in life in order to prevent the development of chronic metabolic disease later in life. PMID:24532817

  7. Chronic exercise preserves lean muscle mass in masters athletes.

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    Wroblewski, Andrew P; Amati, Francesca; Smiley, Mark A; Goodpaster, Bret; Wright, Vonda

    2011-09-01

    Aging is commonly associated with a loss of muscle mass and strength, resulting in falls, functional decline, and the subjective feeling of weakness. Exercise modulates the morbidities of muscle aging. Most studies, however, have examined muscle-loss changes in sedentary aging adults. This leaves the question of whether the changes that are commonly associated with muscle aging reflect the true physiology of muscle aging or whether they reflect disuse atrophy. This study evaluated whether high levels of chronic exercise prevents the loss of lean muscle mass and strength experienced in sedentary aging adults. A cross-section of 40 high-level recreational athletes ("masters athletes") who were aged 40 to 81 years and trained 4 to 5 times per week underwent tests of health/activity, body composition, quadriceps peak torque (PT), and magnetic resonance imaging of bilateral quadriceps. Mid-thigh muscle area, quadriceps area (QA), subcutaneous adipose tissue, and intramuscular adipose tissue were quantified in magnetic resonance imaging using medical image processing, analysis, and visualization software. One-way analysis of variance was used to examine age group differences. Relationships were evaluated using Spearman correlations. Mid-thigh muscle area (P = 0.31) and lean mass (P = 0.15) did not increase with age and were significantly related to retention of mid-thigh muscle area (P lean mass (P = 0.4) and PT. This study contradicts the common observation that muscle mass and strength decline as a function of aging alone. Instead, these declines may signal the effect of chronic disuse rather than muscle aging. Evaluation of masters athletes removes disuse as a confounding variable in the study of lower-extremity function and loss of lean muscle mass. This maintenance of muscle mass and strength may decrease or eliminate the falls, functional decline, and loss of independence that are commonly seen in aging adults.

  8. Osteocalcin is necessary and sufficient to maintain muscle mass in older mice

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    Paula Mera

    2016-10-01

    Full Text Available Objective: A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age. Methods: We examined muscle mass and strength in mice lacking osteocalcin (Ocn−/− or its receptor in all cells (Gprc6a−/− or specifically in myofibers (Gprc6aMck−/− as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days. We also examined protein synthesis in WT and Gprc6a−/− mouse myotubes treated with osteocalcin. Results: We show that osteocalcin signaling in myofibers is necessary to maintain muscle mass in older mice in part because it promotes protein synthesis in myotubes without affecting protein breakdown. We further show that treatment with exogenous osteocalcin for 28 days is sufficient to increase muscle mass of 9-month-old WT mice. Conclusion: This study uncovers that osteocalcin is necessary and sufficient to prevent age-related muscle loss in mice. Author Video: Author Video Watch what authors say about their articles Keywords: Osteocalcin, Muscle mass, Aging

  9. Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice

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    Qiu, Shuiqing; Mintz, James D.; Salet, Christina D.; Han, Weihong; Giannis, Athanassios; Chen, Feng; Yu, Yanfang; Su, Yunchao; Fulton, David J.; Stepp, David W.

    2014-01-01

    Background A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (PMyostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l‐NG‐nitroarginine methyl ester (l‐NAME). Prostacyclin (PGI2)‐ and endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down‐regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l‐NAME. Conclusions Increasing muscle mass by genetic deletion of

  10. Effect of transcutaneous electrical muscle stimulation on postoperative muscle mass and protein synthesis

    DEFF Research Database (Denmark)

    Vinge, O; Edvardsen, L; Jensen, F

    1996-01-01

    In an experimental study, 13 patients undergoing major elective abdominal surgery were given postoperative transcutaneous electrical muscle stimulation (TEMS) to the quadriceps femoris muscle on one leg; the opposite leg served as control. Changes in cross-sectional area (CSA) and muscle protein ...... protein synthesis and muscle mass after abdominal surgery and should be evaluated in other catabolic states with muscle wasting.......In an experimental study, 13 patients undergoing major elective abdominal surgery were given postoperative transcutaneous electrical muscle stimulation (TEMS) to the quadriceps femoris muscle on one leg; the opposite leg served as control. Changes in cross-sectional area (CSA) and muscle protein...... synthesis were assessed by computed tomography and ribosome analysis of percutaneous muscle biopsies before surgery and on the sixth postoperative day. The percentage of polyribosomes in the ribosome suspension decreased significantly (P

  11. How is AMPK activity regulated in skeletal muscles during exercise?

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    AMPK is a metabolic "master" controller activated in skeletal muscle by exercise in a time and intensity dependent manner, and has been implicated in regulating metabolic pathways in muscle during physical exercise. AMPK signaling in skeletal muscle is regulated by several systemic...... and intracellular factors and the regulation of skeletal muscle AMPK in response to exercise is the focus of this review. Specifically, the role of LKB1 and phosphatase PP2C in nucleotide-dependent activation of AMPK, and ionized calcium in CaMKK-dependent activation of AMPK in working muscle is discussed. We also...

  12. Skeletal muscle mass recovery from atrophy in IL-6 knockout mice.

    Science.gov (United States)

    Washington, T A; White, J P; Davis, J M; Wilson, L B; Lowe, L L; Sato, S; Carson, J A

    2011-08-01

    Skeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle's growth and extracellular matrix remodelling response to overload-induced hypertrophy. Insulin-like growth factor-1 (IGF-1) gene expression and related signalling through Akt/mTOR is a critical regulator of muscle mass. The significance of IL-6 expression during the recovery from muscle atrophy is unclear. This study's purpose was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy. Female C57BL/6 [wild type (WT)] and IL-6 knockout (IL-6 KO) mice at 10 weeks of age were assigned to control, HS or HS followed by normal cage ambulation groups. GAS muscle atrophy was induced by 10 days of HS. HS induced a 20% loss of GAS mass in both WT and IL-6 KO mice. HS+7 days of recovery restored WT GAS mass to cage-control values. GAS mass from IL-6 KO mice did not return to cage-control values until HS+14 days of recovery. Both IGF-1 mRNA expression and Akt/mTOR signalling were increased in WT muscle after 1 day of recovery. In IL-6 KO muscle, IGF-1 mRNA expression was decreased and Akt/mTOR signalling was not induced after 1 day of recovery. MyoD and myogenin mRNA expression were both induced in WT muscle after 1 day of recovery, but not in IL-6 KO muscle.   Muscle IL-6 expression appears important for the initial growth response during the recovery from disuse. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  13. Novel biomarkers of changes in muscle mass or muscle pathology

    DEFF Research Database (Denmark)

    Arvanitidis, Athanasios

    healthy individuals and patients with different myopathy diseases, describe the underlying mechanisms of muscle conditions and possibly putative response to an intervention. There were three different studies where biomarkers were applied in this thesis. Study I involved 51 myositis patients (28...

  14. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

    2016-01-01

    Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...... at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals....

  15. Delayed recovery of skeletal muscle mass following hindlimb immobilization in mTOR heterozygous mice.

    Directory of Open Access Journals (Sweden)

    Susan M Lang

    Full Text Available The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/- mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR(+/- mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR(+/- mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR(+/- mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth.

  16. Delayed recovery of skeletal muscle mass following hindlimb immobilization in mTOR heterozygous mice.

    Science.gov (United States)

    Lang, Susan M; Kazi, Abid A; Hong-Brown, Ly; Lang, Charles H

    2012-01-01

    The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/-) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR(+/-) mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR(+/-) mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR(+/-) mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA) during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth.

  17. Inflammatory markers and loss of muscle mass (sarcopenia) and strength

    NARCIS (Netherlands)

    Schaap, Laura A; Pluijm, Saskia M F; Deeg, Dorly J H; Visser, Marjolein

    PURPOSE: The objective of this study was to investigate whether high levels of serum interleukin (IL)-6, C-reactive protein (CRP), and alpha1-antichymotrypsin (ACT) were associated with the loss of muscle strength or muscle mass (sarcopenia) in older persons. SUBJECTS: The study included 986 men and

  18. Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs.

    Science.gov (United States)

    Joyner, Michael J; Casey, Darren P

    2015-04-01

    This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans. Copyright © 2015 the American Physiological Society.

  19. Association between muscle mass and a single measurement of ...

    African Journals Online (AJOL)

    cause mortality significantly. It is strongly associated with the risk of heart attack, coronary artery disease, cardiovascular disease, stroke and liver disease. The relationship between muscle mass and a diagnosis of hypertension in a sample of ...

  20. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Tingqing Guo

    Full Text Available Myostatin (Mstn is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/- mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/- mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/- mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/- mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/- mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/- mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

  1. Identification of microRNAs linked to regulators of muscle protein synthesis and regeneration in young and old skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Evelyn Zacharewicz

    Full Text Available BACKGROUND: Over the course of ageing there is a natural and progressive loss of skeletal muscle mass. The onset and progression of age-related muscle wasting is associated with an attenuated activation of Akt-mTOR signalling and muscle protein synthesis in response to anabolic stimuli such as resistance exercise. MicroRNAs (miRNAs are novel and important post-transcriptional regulators of numerous cellular processes. The role of miRNAs in the regulation of muscle protein synthesis following resistance exercise is poorly understood. This study investigated the changes in skeletal muscle miRNA expression following an acute bout of resistance exercise in young and old subjects with a focus on the miRNA species predicted to target Akt-mTOR signalling. RESULTS: Ten young (24.2±0.9 years and 10 old (66.6±1.1 years males completed an acute resistance exercise bout known to maximise muscle protein synthesis, with muscle biopsies collected before and 2 hours after exercise. We screened the expression of 754 miRNAs in the muscle biopsies and found 26 miRNAs to be regulated with age, exercise or a combination of both factors. Nine of these miRNAs are highly predicted to regulate targets within the Akt-mTOR signalling pathway and 5 miRNAs have validated binding sites within the 3' UTRs of several members of the Akt-mTOR signalling pathway. The miR-99/100 family of miRNAs notably emerged as potentially important regulators of skeletal muscle mass in young and old subjects. CONCLUSION: This study has identified several miRNAs that were regulated with age or with a single bout of resistance exercise. Some of these miRNAs were predicted to influence Akt-mTOR signalling, and therefore potentially skeletal muscle mass. These miRNAs should be considered as candidate targets for in vivo modulation.

  2. Regulation of PDH, GS and insulin signalling in skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    of inflammation on resting and exercise-induced PDH regulation in human skeletal muscle and 4) The effect of IL-6 on PDH regulation in mouse skeletal muscle. Study I demonstrated that bed rest–induced insulin resistance was associated with reduced insulinstimulated GS activity and Akt signaling as well...

  3. Relation between body mass index percentile and muscle strength ...

    African Journals Online (AJOL)

    Relation between body mass index percentile and muscle strength and endurance. ... Egyptian Journal of Medical Human Genetics ... They were divided into three groups according to their body mass index percentile where group (a) is equal to or more than 5% percentile yet less than 85% percentile, group (b) is equal to ...

  4. Correlation between Body Mass Index, Gender, and Skeletal Muscle Mass Cut off Point in Bandung

    OpenAIRE

    Richi Hendrik Wattimena; Vitriana; Irma Ruslina Defi

    2017-01-01

    Objective: To determine the average skeletal muscle mass (SMM) value in young adults as a reference population; to analyze the correlation of gender, and body mass index to the cut off point; and to determine skeletal muscle mass cut off points of population in Bandung, Indonesia. Methods: This was a cross-sectional study involving 199 participants, 122 females and 77 males. The sampling technique used was the multistage random sampling. The participants were those who lived in four ma...

  5. [Variation of muscle mass and weight in critical patient].

    Science.gov (United States)

    Valls-Matarín, J; del Cotillo-Fuente, M; Grané-Mascarell, N; Quintana, S

    2015-01-01

    Quantify the muscle mass and body weight variation in critically ill patients and to identify associated factors. A descriptive follow-up study. Data for demographic variables, body weight, fluid balance, daily kilocalories, the amount of sedation and muscle relaxants received and motor physiotherapy applied were collected. Three consecutive measurements were performed in the brachial biceps and quadriceps rectus by using ultrasound, upon admission and every 5 days until discharge. 68 patients were included. Average age was of 73.5 [57-78,5] years. The median length of stay was 9.5 [5.5 -15] days. The median 16 (SD=5.7) daily kilocalories per kg/weight, 91.2% received sedation, 44.1% received muscle relaxants and 20% received physiotherapy. The patients presented a muscle wasting of 4.9 (SD=3.9)mm, p <.001 in the brachial biceps and 5.6 (SD=4.8)mm, p <.001 in the quadriceps rectus. Regression analysis selected the length of stay and the muscle relaxants are the most influential variables in the brachial biceps muscle wasting (R2=0.4), and length of stay as the most influential in the quadriceps rectus muscle wasting (R2=0.3). Patient's mean body weight on admission was of 81.1 (SD=15)kg and 81.2 (SD=14.2)kg on discharge, p=.95. The critically ill patient presents a significant muscle waste related with the length of stay and the treatment received with muscle relaxants. Patients are being discharged with a similar body weight to which they were admitted but with a significant reduction of muscle mass. Copyright © 2014 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

  6. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression

    DEFF Research Database (Denmark)

    Davidsen, Peter K; Gallagher, Iain J; Hartman, Joseph W

    2011-01-01

    MicroRNAs (miRNA), small noncoding RNA molecules, may regulate protein synthesis, while resistance exercise training (RT) is an efficient strategy for stimulating muscle protein synthesis in vivo. However, RT increases muscle mass, with a very wide range of effectiveness in humans. We therefore...... determined the expression level of 21 abundant miRNAs to determine whether variation in these miRNAs was able to explain the variation in RT-induced gains in muscle mass. Vastus lateralis biopsies were obtained from the top and bottom ~20% of responders from 56 young men who undertook a 5 day/wk RT program...... for 12 wk. Training-induced muscle mass gain was determined by dual-energy X-ray absorptiometry, and fiber size was evaluated by histochemistry. The expression level of each miRNA was quantified using TaqMan-based quantitative PCR, with the analysis carried out in a blinded manner. Gene ontology...

  7. Regulation of skeletal muscle glycogenolysis during exercise

    DEFF Research Database (Denmark)

    Hargreaves, M; Richter, Erik

    1988-01-01

    Muscle-glycogen breakdown during exercise is influenced by both local and systemic factors. Contractions per se increase glycogenolysis via a calcium-induced, transient increase in the activity of phosphorylase a, and probably also via increased concentrations of Pi. In fast-twitch muscle...... in contracting muscle by increasing the phosphorylase a activity via increased cyclic AMP production. The availability of blood-borne substrates may also influence muscle glycogenolysis and, therefore, exercise performance......., increases in the AMP and IMP levels may increase phosphorylase activity. The rate of muscle-glycogen breakdown during exercise depends on the pre-exercise glycogen concentration and is also influenced by hormones. Insulin may inhibit glycogen breakdown, whereas epinephrine enhances the rate of glycogen use...

  8. Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in Elderly

    Directory of Open Access Journals (Sweden)

    Britta Wåhlin-Larsson

    2017-11-01

    Full Text Available Background/Aims: Mechanisms underlying the relationship between systemic inflammation and age-related decline in muscle mass are poorly defined. The purpose of this work was to investigate the relationship between the systemic inflammatory marker CRP and muscle mass in elderly and to identify mechanisms by which CRP mediates its effects on skeletal muscle, in-vitro. Methods: Muscle mass and serum CRP level were determined in a cohort of 118 older women (67±1.7 years. Human muscle cells were differentiated into myotubes and were exposed to CRP. The size of myotubes was determined after immunofluorescent staining using troponin. Muscle protein synthesis was assessed using stable isotope tracers and key signalling pathways controlling protein synthesis were determined using western-blotting. Results: We observed an inverse relationship between circulating CRP level and muscle mass (β= -0.646 (95% CI: -0.888, -0.405 p<0.05 and demonstrated a reduction (p < 0.05 in the size of human myotubes exposed to CRP for 72 h. We next showed that this morphological change was accompanied by a CRP-mediated reduction (p < 0.05 in muscle protein fractional synthetic rate of human myotubes exposed to CRP for 24 h. We also identified a CRP-mediated increased phosphorylation (p<0.05 of regulators of cellular energy stress including AMPK and downstream targets, raptor and ACC-β, together with decreased phosphorylation of Akt and rpS6, which are important factors controlling protein synthesis. Conclusion: This work established for the first time mechanistic links by which chronic elevation of CRP can contribute to age-related decline in muscle function.

  9. Regulation of exercise-induced lipid metabolism in skeletal muscle

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting; Kiens, Bente

    2014-01-01

    Exercise increases the utilization of lipids in muscle. The sources of lipids are long-chain fatty acids taken up from the plasma and fatty acids released from stores of intramuscular triacylglycerol by the action of intramuscular lipases. In the present review, we focus on the role of fatty acid...... binding proteins, particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in the exercise- and contraction-induced increase in uptake of long-chain fatty acids in muscle. The FAT/CD36 translocates from intracellular depots to the surface membrane upon initiation of exercise/muscle...... triglyceride lipase in regulation of muscle lipolysis. Although the molecular regulation of the lipases in muscle is not understood, it is speculated that intramuscular lipolysis may be regulated in part by the availability of the plasma concentration of long-chain fatty acids....

  10. Skeletal muscle deiodinase type 2 regulation during illness in mice

    NARCIS (Netherlands)

    Kwakkel, J.; van Beeren, H. C.; Ackermans, M. T.; Platvoet-ter Schiphorst, M. C.; Fliers, E.; Wiersinga, W. M.; Boelen, A.

    2009-01-01

    We have previously shown that skeletal muscle deiodinase type 2 (D2) mRNA (listed as Dio2 in MGI Database) is up-regulated in an animal model of acute illness. However, human Studies on the expression Of muscle D2 during illness report conflicting data. Therefore, we evaluated the expression of

  11. HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration

    Science.gov (United States)

    Hong, Peng; Chen, Kang; Huang, Bihui; Liu, Min; Cui, Miao; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Barton, Elisabeth R.; Jiang, Xian-Cheng; Siddiqui, M.A.Q.

    2012-01-01

    The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases. PMID:23023707

  12. Within-Winter Flexibility in Muscle Masses, Myostatin, and Cellular Aerobic Metabolic Intensity in Passerine Birds.

    Science.gov (United States)

    Swanson, David L; King, Marisa O; Culver, William; Zhang, Yufeng

    Metabolic rates of passerine birds are flexible traits that vary both seasonally and among and within winters. Seasonal variation in summit metabolic rates (M sum = maximum thermoregulatory metabolism) in birds is consistently correlated with changes in pectoralis muscle and heart masses and sometimes with variation in cellular aerobic metabolic intensity, so these traits might also be associated with shorter-term, within-winter variation in metabolic rates. To determine whether these mechanisms are associated with within-winter variation in M sum , we examined the effects of short-term (ST; 0-7 d), medium-term (MT; 14-30 d), and long-term (LT; 30-yr means) temperature variables on pectoralis muscle and heart masses, pectoralis expression of the muscle-growth inhibitor myostatin and its metalloproteinase activators TLL-1 and TLL-2, and pectoralis and heart citrate synthase (CS; an indicator of cellular aerobic metabolic intensity) activities for two temperate-zone resident passerines, house sparrows (Passer domesticus) and dark-eyed juncos (Junco hyemalis). For both species, pectoralis mass residuals were positively correlated with ST temperature variables, suggesting that cold temperatures resulted in increased turnover of pectoralis muscle, but heart mass showed little within-winter variation for either species. Pectoralis mRNA and protein expression of myostatin and the TLLs were only weakly correlated with ST and MT temperature variables, which is largely consistent with trends in muscle masses for both species. Pectoralis and heart CS activities showed weak and variable trends with ST temperature variables in both species, suggesting only minor effects of temperature variation on cellular aerobic metabolic intensity. Thus, neither muscle or heart masses, regulation by the myostatin system, nor cellular aerobic metabolic intensity varied consistently with winter temperature, suggesting that other factors regulate within-winter metabolic variation in these birds.

  13. Myoglobin plasma level related to muscle mass and fiber composition: a clinical marker of muscle wasting?

    Science.gov (United States)

    Weber, Marc-André; Kinscherf, Ralf; Krakowski-Roosen, Holger; Aulmann, Michael; Renk, Hanna; Künkele, Annette; Edler, Lutz; Kauczor, Hans-Ulrich; Hildebrandt, Wulf

    2007-08-01

    Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study.

  14. Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass

    DEFF Research Database (Denmark)

    Nielsen, Anders Rinnov; Hojman, Pernille; Erikstrup, Christian

    2008-01-01

    Objective: IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way...

  15. Muscle hypertrophy: a narrative review on training principles for increasing muscle mass

    OpenAIRE

    Howe, Louis; Read, Paul; Waldron, Mark

    2017-01-01

    Developing muscle cross-sectional area has the potential to enhance performance for many athletes. Because emerging evidence challenges traditional beliefs regarding the prescription of hypertrophy-focused training programs, this review provides an overview of the current literature relating, specifically, to programming variables. Evidence-based recommendations are provided for the design of effective resistance-training programs, with the goal of increasing an athlete's skeletal muscle mass.

  16. Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression.

    Science.gov (United States)

    Goljanek-Whysall, Katarzyna; Iwanejko, Lesley A; Vasilaki, Aphrodite; Pekovic-Vaughan, Vanja; McDonagh, Brian

    2016-08-01

    Ageing is associated with a progressive loss of skeletal muscle mass, quality and function-sarcopenia, associated with reduced independence and quality of life in older generations. A better understanding of the mechanisms, both genetic and epigenetic, underlying this process would help develop therapeutic interventions to prevent, slow down or reverse muscle wasting associated with ageing. Currently, exercise is the only known effective intervention to delay the progression of sarcopenia. The cellular responses that occur in muscle fibres following exercise provide valuable clues to the molecular mechanisms regulating muscle homoeostasis and potentially the progression of sarcopenia. Redox signalling, as a result of endogenous generation of ROS/RNS in response to muscle contractions, has been identified as a crucial regulator for the adaptive responses to exercise, highlighting the redox environment as a potentially core therapeutic approach to maintain muscle homoeostasis during ageing. Further novel and attractive candidates include the manipulation of microRNA expression. MicroRNAs are potent gene regulators involved in the control of healthy and disease-associated biological processes and their therapeutic potential has been researched in the context of various disorders, including ageing-associated muscle wasting. Finally, we discuss the impact of the circadian clock on the regulation of gene expression in skeletal muscle and whether disruption of the peripheral muscle clock affects sarcopenia and altered responses to exercise. Interventions that include modifying altered redox signalling with age and incorporating genetic mechanisms such as circadian- and microRNA-based gene regulation, may offer potential effective treatments against age-associated sarcopenia.

  17. Leg blood flow is impaired during small muscle mass exercise in patients with COPD

    DEFF Research Database (Denmark)

    Iepsen, Ulrik Winning; Munch, Gregers Druedal Wibe; Rugbjerg, Mette

    2017-01-01

    to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggests that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1.......Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with COPD. We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee...... the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response...

  18. Building muscle: molecular regulation of myogenesis.

    Science.gov (United States)

    Bentzinger, C Florian; Wang, Yu Xin; Rudnicki, Michael A

    2012-02-01

    The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.

  19. Electromyogram refinement using muscle synergy based regulation of uncertain information.

    Science.gov (United States)

    Min, Kyuengbo; Shin, Duk; Lee, Jongho; Kakei, Shinji

    2018-04-27

    Electromyogram signal (EMG) measurement frequently experiences uncertainty attributed to issues caused by technical constraints such as cross talk and maximum voluntary contraction. Due to these problems, individual EMGs exhibit uncertainty in representing their corresponding muscle activations. To regulate this uncertainty, we proposed an EMG refinement, which refines EMGs with regulating the contribution redundancy of the signals from EMGs to approximating torques through EMG-driven torque estimation (EDTE) using the muscular skeletal forward dynamic model. To regulate this redundancy, we must consider the synergistic contribution redundancy of muscles, including "unmeasured" muscles, to approximating torques, which primarily causes redundancy of EDTE. To suppress this redundancy, we used the concept of muscle synergy, which is a key concept of analyzing the neurophysiological regulation of contribution redundancy of muscles to exerting torques. Based on this concept, we designed a muscle-synergy-based EDTE as a framework for EMG refinement, which regulates the abovementioned uncertainty of individual EMGs in consideration of unmeasured muscles. In achieving the proposed EMG refinement, the most considerable point is to suppress a large change such as overestimation attributed to enhancement of the contribution of particular muscles to estimating torques. Therefore it is reasonable to refine EMGs by minimizing the change in EMGs. To evaluate this model, we used a Bland-Altman plot, which quantitatively evaluates the proportional bias of refined signals to EMGs. Through this evaluation, we showed that the proposed EDTE minimizes the bias while approximating torques. Therefore this minimization optimally regulates the uncertainty of EMGs and thereby leads to optimal EMG refinement. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy.

    Science.gov (United States)

    Jeong, Juseong; Park, Choon-Ho; Kim, Inbo; Kim, Young-Ho; Yoon, Jae-Min; Kim, Kwang-Soo; Kim, Jong-Bae

    2017-01-21

    Korean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle. We examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model. Interestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice. Our results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.

  1. Regulation of Blood Flow in Contracting Skeletal Muscle in Aging

    DEFF Research Database (Denmark)

    Piil, Peter Bergmann

    Oxygen delivery to skeletal muscle is regulated precisely to match the oxygen demand; however, with aging the regulation of oxygen delivery during exercise is impaired. The present thesis investigated mechanisms underlying the age-related impairment in regulation of blood flow and oxygen delivery......GMP) was used as intervention, and skeletal muscle blood flow, oxygen delivery, and functional sympatholysis was examined. The two studies included 53 healthy, habitually active, male subjects. All subjects participated in an experimental day in which femoral arterial blood flow and blood pressure were assessed...... that improving sympatholytic capacity by training may be a slower process in older than in young men. In conclusion, this thesis provides new important knowledge related to the regulation of skeletal muscle blood flow in aging. Specifically, it demonstrates that changes in cGMP signaling is an underlying cause...

  2. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...... hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation...

  3. Diagnostic ultrasound estimates of muscle mass and muscle quality discriminate between women with and without sarcopenia

    Directory of Open Access Journals (Sweden)

    Catheeja eIsmail

    2015-10-01

    Full Text Available Introduction: Age-related changes in muscle mass and muscle tissue composition contribute to diminished strength in older adults. The objectives of this study are to examine if an assessment method using mobile diagnostic ultrasound augments well-known determinants of lean body mass (LBM to aid sarcopenia staging, and if a sonographic measure of muscle quality is associated with muscle performance.Methods: Twenty community-dwelling female subjects participated in the study (age = 43.4 ±20.9 years; BMI: 23.8, interquartile range: 8.5. Dual energy X-ray absorptiometry (DXA and diagnostic ultrasound morphometry were used to estimate LBM. Muscle tissue quality was estimated via the echogenicity using grayscale histogram analysis. Peak force was measured with grip dynamometry and scaled for body size. Bivariate and multiple regression analyses were used to determine the association of the predictor variables with appendicular lean mass (aLM/ht2, and examine the relationship between scaled peak force values and muscle echogenicity. The sarcopenia LBM cut point value of 6.75 kg/m2 determined participant assignment into the Normal LBM and Low LBM subgroups.Results: The selected LBM predictor variables were body mass index (BMI, ultrasound morphometry, and age. Although BMI exhibited a significant positive relationship with aLM/ht2 (adj. R2 = .61, p < .001, the strength of association improved with the addition of ultrasound morphometry and age as predictor variables (adj. R2 = .85, p < .001. Scaled peak force was associated with age and echogenicity (adj. R2 = .53, p < .001, but not LBM. The Low LBM subgroup of women (n = 10 had higher scaled peak force, lower BMI, and lower echogenicity values in comparison to the Normal LBM subgroup (n = 10; p < .05.Conclusions: Diagnostic ultrasound morphometry values are associated with LBM, and improve the BMI predictive model for aLM/ht2 in women. In addition, ultrasound proxy measures of muscle quality are more

  4. Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Marcelo G. Pereira

    2017-12-01

    Full Text Available Skeletal muscle mass is a result of the balance between protein breakdown and protein synthesis. It has been shown that multiple conditions of muscle atrophy are characterized by the common regulation of a specific set of genes, termed atrogenes. It is not known whether various models of muscle hypertrophy are similarly regulated by a common transcriptional program. Here, we characterized gene expression changes in three different conditions of muscle growth, examining each condition during acute and chronic phases. Specifically, we compared the transcriptome of Extensor Digitorum Longus (EDL muscles collected (1 during the rapid phase of postnatal growth at 2 and 4 weeks of age, (2 24 h or 3 weeks after constitutive activation of AKT, and (3 24 h or 3 weeks after overload hypertrophy caused by tenotomy of the Tibialis Anterior muscle. We observed an important overlap between significantly regulated genes when comparing each single condition at the two different timepoints. Furthermore, examining the transcriptional changes occurring 24 h after a hypertrophic stimulus, we identify an important role for genes linked to a stress response, despite the absence of muscle damage in the AKT model. However, when we compared all different growth conditions, we did not find a common transcriptional fingerprint. On the other hand, all conditions showed a marked increase in mTORC1 signaling and increased ribosome biogenesis, suggesting that muscle growth is characterized more by translational, than transcriptional regulation.

  5. Peripheral endocannabinoids regulate skeletal muscle development and maintenance

    Directory of Open Access Journals (Sweden)

    Dongjiao Zhao

    2010-12-01

    Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

  6. PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.

    Directory of Open Access Journals (Sweden)

    Estibaliz Castillero

    Full Text Available FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions.

  7. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Søren; Scheele, Camilla; Yfanti, Christina

    2010-01-01

    Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus...... lateralis of healthy young males (n = 10) in relation to a hyperinsulinaemic–euglycaemic clamp as well as acute endurance exercise before and after 12 weeks of endurance training. The subjects increased their endurance capacity, VO2max (l min-1) by 17.4% (P improved insulin sensitivity by 19......, but their role in regulating human skeletal muscle adaptation remains unknown....

  8. ASIC PROTEINS REGULATE SMOOTH MUSCLE CELL MIGRATION

    OpenAIRE

    Grifoni, Samira C.; Jernigan, Nikki L.; Hamilton, Gina; Drummond, Heather A.

    2007-01-01

    The purpose of the present study was to investigate Acid Sensing Ion Channel (ASIC) protein expression and importance in cellular migration. We recently demonstrated Epithelial Na+ Channel (ENaC) proteins are required for vascular smooth muscle cell (VSMC) migration, however the role of the closely related ASIC proteins has not been addressed. We used RT-PCR and immunolabeling to determine expression of ASIC1, ASIC2, ASIC3 and ASIC4 in A10 cells. We used small interference RNA to silence indi...

  9. Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet; Bertholdt, Lærke; Joensen, Ella

    2015-01-01

    in combination with exercise training (HFD ExTr) for 16 weeks. RESULTS: Total fat mass increased (P mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP......OBJECTIVE: To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. METHODS: Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD.......05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P mass through regulation of glucose uptake capacity as well as lipogenic...

  10. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  11. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  12. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  13. ASIC proteins regulate smooth muscle cell migration.

    Science.gov (United States)

    Grifoni, Samira C; Jernigan, Nikki L; Hamilton, Gina; Drummond, Heather A

    2008-03-01

    The purpose of the present study was to investigate Acid Sensing Ion Channel (ASIC) protein expression and importance in cellular migration. We recently demonstrated that Epithelial Na(+)Channel (ENaC) proteins are required for vascular smooth muscle cell (VSMC) migration; however, the role of the closely related ASIC proteins has not been addressed. We used RT-PCR and immunolabeling to determine expression of ASIC1, ASIC2, ASIC3 and ASIC4 in A10 cells. We used small interference RNA to silence individual ASIC expression and determine the importance of ASIC proteins in wound healing and chemotaxis (PDGF-bb)-initiated migration. We found ASIC1, ASIC2, and ASIC3, but not ASIC4, expression in A10 cells. ASIC1, ASIC2, and ASIC3 siRNA molecules significantly suppressed expression of their respective proteins compared to non-targeting siRNA (RISC) transfected controls by 63%, 44%, and 55%, respectively. Wound healing was inhibited by 10, 20, and 26% compared to RISC controls following suppression of ASIC1, ASIC2, and ASIC3, respectively. Chemotactic migration was inhibited by 30% and 45%, respectively, following suppression of ASIC1 and ASIC3. ASIC2 suppression produced a small, but significant, increase in chemotactic migration (4%). Our data indicate that ASIC expression is required for normal migration and may suggest a novel role for ASIC proteins in cellular migration.

  14. Epigenetic Regulators Modulate Muscle Damage in Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Bajanca, Fernanda; Vandel, Laurence

    2017-12-21

    Histone acetyl transferases (HATs) and histone deacetylases (HDAC) control transcription during myogenesis. HDACs promote chromatin condensation, inhibiting gene transcription in muscle progenitor cells until myoblast differentiation is triggered and HDACs are released. HATs, namely CBP/p300, activate myogenic regulatory and elongation factors promoting myogenesis. HDAC inhibitors are known to improve regeneration in dystrophic muscles through follistatin upregulation. However, the potential of directly modulating HATs remains unexplored. We tested this possibility in a well-known zebrafish model of Duchenne muscular dystrophy. Interestingly, CBP/p300 transcripts were found downregulated in the absence of Dystrophin. While investigating CBP rescuing potential we observed that dystrophin-null embryos overexpressing CBP actually never show significant muscle damage, even before a first regeneration cycle could occur. We found that the pan-HDAC inhibitor trichostatin A (TSA) also prevents early muscle damage, however the single HAT CBP is as efficient even in low doses. The HAT domain of CBP is required for its full rescuing ability. Importantly, both CBP and TSA prevent early muscle damage without restoring endogenous CBP/p300 neither increasing follistatin transcripts. This suggests a new mechanism of action of epigenetic regulators protecting dystrophin-null muscle fibres from detaching, independent from the known improvement of regeneration upon damage of HDACs inhibitors. This study builds supporting evidence that epigenetic modulators may play a role in determining the severity of muscle dystrophy, controlling the ability to resist muscle damage. Determining the mode of action leading to muscle protection can potentially lead to new treatment options for muscular dystrophies in the future.

  15. Appendicular Skeletal Muscle Mass Reference Values and the Peak Muscle Mass to Identify Sarcopenia among Iranian Healthy Population.

    Science.gov (United States)

    Shafiee, Gita; Ostovar, Afshin; Heshmat, Ramin; Keshtkar, Abbas Ali; Sharifi, Farshad; Shadman, Zhaleh; Nabipour, Iraj; Soltani, Akbar; Larijani, Bagher

    2018-01-01

    Sacopenia is a common problem in elderly with the adverse outcomes. The objective of this study was to estimate the peak appendicular skeletal muscle mass (ASM) and age of its attainment by sex among the Iranian population. A total of 691 men and women aged 18-94 years participated in this cross-sectional, population-based study in Bushehr, Iran. ASM was measured by dual X-ray absorptiometry. Cutoff points for men and women were established considering two standard deviations (SDs) below the mean values of the skeletal muscle index (SMI) for young reference groups. The relationship between ASM and age was described by the second-degree regression models. Two SDs below the mean SMIs of reference groups were as cutoff values of low muscle mass in Iranian population. The peak ASM values were 21.35 ± 0.12 Kg and 13.68 ± 0.10 Kg, and the age at peak ASM were 26 (24-28) years and 34 (33-35) years for men and women, respectively. Mean and SD of SMI in those ages were 7.01 ± 0.02 Kg/m 2 and 5.44 ± 0.02 Kg/m 2 among men and women, respectively. Calculated cutoff values of low muscle mass among the Iranian population were 7.0 Kg/m 2 and 5.4 Kg/m 2 among men and women, respectively. Iranian reference values of SMI for both genders were similar to Asia Working Group for Sarcopenia recommendation and lower than the United States and European values. Further studies from different nations and the Middle East countries are needed to obtain reference values for populations, enabling the researchers for comparison and also more valid reports on sarcopenia prevalence.

  16. Psoas muscle cross-sectional area as a measure of whole body lean muscle mass in maintenance hemodialysis patients

    Science.gov (United States)

    Morrell, Glen R.; Ikizler, Talat A.; Chen, Xiaorui; Heilbrun, Marta E.; Wei, Guo; Boucher, Robert; Beddhu, Srinivasan

    2016-01-01

    Objective We investigate whether psoas or paraspinous muscle area measured on a single L4–5 image is a useful measure of whole lean body mass compared to dedicated mid-thigh magnetic resonance imaging (MRI). Design Observational study. Setting Outpatient dialysis units and a research clinic. Subjects 105 adult participants on maintenance hemodialysis. No control group was used. Exposure variables Psoas muscle area, paraspinous muscle area, and mid-thigh muscle area (MTMA) were measured by MRI. Main outcome measure Lean body mass was measured by dual-energy absorptiometry (DEXA) scan. Results In separate multivariable linear regression models, psoas, paraspinous, and mid-thigh muscle area were associated with increase in lean body mass. In separate multivariate logistic regression models, c-statistics for diagnosis of sarcopenia (defined as lean body mass) were 0.69 for paraspinous muscle area, 0.81 for psoas muscle area, and 0.89 for mid-thigh muscle area. With sarcopenia defined as lean body mass, the corresponding c-statistics were 0.71, 0.92, and 0.94. Conclusions We conclude that psoas muscle area provides a good measure of whole body muscle mass, better than paraspinous muscle area but slightly inferior to mid thigh measurement. Hence, in body composition studies a single axial MR image at the L4–L5 level can be used to provide information on both fat and muscle and may eliminate the need for time-consuming measurement of muscle area in the thigh. PMID:26994780

  17. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    Science.gov (United States)

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

  18. Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.

    Science.gov (United States)

    Buehring, B; Siglinsky, E; Krueger, D; Evans, W; Hellerstein, M; Yamada, Y; Binkley, N

    2018-03-01

    DXA-measured lean mass is often used to assess muscle mass but has limitations. Thus, we compared DXA lean mass with two novel methods-bioelectric impedance spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did not measure lean mass similarly and the correlation with muscle biomarkers/function varied. Muscle function tests predict adverse health outcomes better than lean mass measurement. This may reflect limitations of current mass measurement methods. Newer approaches, e.g., bioelectric impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle mass would better correlate with function and bone/muscle biomarkers than DXA measured lean mass. Evaluations of muscle/lean mass, function, and serum biomarkers were obtained in older community-dwelling adults. Mass was assessed by DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump power were examined. Potential muscle/bone serum biomarkers were measured. Mass measurements were compared with functional and serum data using regression analyses; differences between techniques were determined by paired t tests. Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years. The lean/muscle mass assessments were correlated (.57-.88) but differed (p Lean mass measures were unrelated to the serum biomarkers measured. These three methodologies do not similarly measure muscle/lean mass and should not be viewed as being equivalent. Functional tests assessing maximal muscle strength/power (grip strength and jump power) correlated with all mass measures whereas gait speed was not. None of the selected serum measures correlated with mass. Efforts to optimize muscle mass assessment and identify their relationships with health outcomes are needed.

  19. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women : the Health ABC Study

    NARCIS (Netherlands)

    Visser, Marjolein; Pahor, Marco; Taaffe, Dennis R; Goodpaster, Bret H; Simonsick, Eleanor M; Newman, Anne B; Nevitt, Michael; Harris, Tamara B

    BACKGROUND: A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show a relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers of inflammation are associated with muscle mass and

  20. Fat-Free Mass and Skeletal Muscle Mass Five Years After Bariatric Surgery.

    Science.gov (United States)

    Davidson, Lance E; Yu, Wen; Goodpaster, Bret H; DeLany, James P; Widen, Elizabeth; Lemos, Thaisa; Strain, Gladys W; Pomp, Alfons; Courcoulas, Anita P; Lin, Susan; Janumala, Isaiah; Thornton, John C; Gallagher, Dympna

    2018-07-01

    This study investigated changes in fat-free mass (FFM) and skeletal muscle 5 years after surgery in participants from the Longitudinal Assessment of Bariatric Surgery-2 trial. A three-compartment model assessed FFM, and whole-body magnetic resonance imaging (MRI) quantified skeletal muscle mass prior to surgery (T0) and 1 year (T1), 2 years (T2), and 5 years (T5) postoperatively in 93 patients (85% female; 68% Caucasian; age 44.2 ± 11.6 years) who underwent gastric bypass (RYGB), sleeve gastrectomy, or adjustable gastric band. Repeated-measures mixed models were used to analyze the data. Significant weight loss occurred across all surgical groups in females from T0 to T1. FFM loss from T0 to T1 was greater after RYGB (mean ± SE: -6.9 ± 0.6 kg) than adjustable gastric band (-3.5 ± 1.4 kg; P FFM (-3.3 ± 0.7 kg; P FFM loss while maintaining FFM and skeletal muscle from T1 to T5. Between 1 and 5 years following common bariatric procedures, FFM and skeletal muscle are maintained or decrease minimally. The changes observed in FFM and muscle during the follow-up phase may be consistent with aging. © 2018 The Obesity Society.

  1. Association of low back pain with muscle stiffness and muscle mass of the lumbar back muscles, and sagittal spinal alignment in young and middle-aged medical workers.

    Science.gov (United States)

    Masaki, Mitsuhiro; Aoyama, Tomoki; Murakami, Takashi; Yanase, Ko; Ji, Xiang; Tateuchi, Hiroshige; Ichihashi, Noriaki

    2017-11-01

    Muscle stiffness of the lumbar back muscles in low back pain (LBP) patients has not been clearly elucidated because quantitative assessment of the stiffness of individual muscles was conventionally difficult. This study aimed to examine the association of LBP with muscle stiffness assessed using ultrasonic shear wave elastography (SWE) and muscle mass of the lumbar back muscle, and spinal alignment in young and middle-aged medical workers. The study comprised 23 asymptomatic medical workers [control (CTR) group] and 9 medical workers with LBP (LBP group). Muscle stiffness and mass of the lumbar back muscles (lumbar erector spinae, multifidus, and quadratus lumborum) in the prone position were measured using ultrasonic SWE. Sagittal spinal alignment in the standing and prone positions was measured using a Spinal Mouse. The association with LBP was investigated by multiple logistic regression analysis with a forward selection method. The analysis was conducted using the shear elastic modulus and muscle thickness of the lumbar back muscles, and spinal alignment, age, body height, body weight, and sex as independent variables. Multiple logistic regression analysis showed that muscle stiffness of the lumbar multifidus muscle and body height were significant and independent determinants of LBP, but that muscle mass and spinal alignment were not. Muscle stiffness of the lumbar multifidus muscle in the LBP group was significantly higher than that in the CTR group. The results of this study suggest that LBP is associated with muscle stiffness of the lumbar multifidus muscle in young and middle-aged medical workers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Gender-Dimorphic Regulation of Skeletal Muscle Proteins in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Minji Choi

    2013-03-01

    Full Text Available Background: Despite the fact that sexual differences increase diabetic risk and contribute to the need for gender-specific care, there remain contradictory results as to whether or not sexual dimorphism increases susceptibility to the development of type 1 diabetes mellitus. Methods: To examine gender-dimorphic regulation of skeletal muscle proteins between healthy control and STZ-induced diabetic rats of both genders, we performed differential proteome analysis using two-dimensional electrophoresis combined with mass spectrometry. Results: Animal experiments revealed that STZ treatment rendered female rats more susceptible to induction of diabetes than their male littermates with significantly lower plasma insulin levels due to hormonal regulation. Proteomic analysis of skeletal muscle identified a total of 21 proteins showing gender-dimorphic differential expression patterns between healthy controls and diabetic rats. Most interestingly, gender-specific proteome comparison showed that male and female rats displayed differential regulation of proteins involved in muscle contraction, carbohydrate, and lipid metabolism, as well as oxidative phosphorylation and cellular stress. Conclusion: The current proteomic study revealed that impaired protein regulation was more prominent in the muscle tissue of female diabetic rats, which were more susceptible to STZ-induced diabetes. We expect that the present proteomic data can provide valuable information for evidence-based gender-specific treatment of diabetes.

  3. A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys.

    Science.gov (United States)

    St Andre, Michael; Johnson, Mark; Bansal, Prashant N; Wellen, Jeremy; Robertson, Andrew; Opsahl, Alan; Burch, Peter M; Bialek, Peter; Morris, Carl; Owens, Jane

    2017-11-09

    The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice. Therefore, myostatin blockade via a specific antibody could ameliorate the muscle weakness in DMD patients by increasing skeletal muscle mass and function, thereby reducing patients' functional decline. A murine anti-myostatin antibody, mRK35, and its humanized analog, domagrozumab, were developed and their ability to inhibit several TGB-β ligands was measured using a cell-based Smad-activity reporter system. Normal and mdx mice were treated with mRK35 to examine the antibody's effect on body weight, lean mass, muscle weights, grip strength, ex vivo force production, and fiber size. The humanized analog (domagrozumab) was tested in non-human primates (NHPs) for changes in skeletal muscle mass and volume as well as target engagement via modulation of circulating myostatin. Both the murine and human antibodies are specific and potent inhibitors of myostatin and GDF11. mRK35 is able to increase body weight, lean mass, and muscle weights in normal mice. In mdx mice, mRK35 significantly increased body weight, muscle weights, grip strength, and ex vivo force production in the extensor digitorum longus (EDL) muscle. Further, tibialis anterior (TA) fiber size was significantly increased. NHPs treated with domagrozumab demonstrated a dose-dependent increase in lean mass and muscle volume and exhibited increased circulating levels of myostatin demonstrating target engagement. We demonstrated that the potent anti-myostatin antibody mRK35 and

  4. A low muscle mass increases mortality in compensated cirrhotic patients with sepsis.

    Science.gov (United States)

    Lucidi, Cristina; Lattanzi, Barbara; Di Gregorio, Vincenza; Incicco, Simone; D'Ambrosio, Daria; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

    2018-05-01

    Severe infections and muscle wasting are both associated to poor outcome in cirrhosis. A possible synergic effect of these two entities in cirrhotic patients has not been previously investigated. We aimed at analysing if a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis. Consecutive cirrhotic patients hospitalized for sepsis were enrolled in the study. Patients were classified for the severity of liver impairment (Child-Pugh class) and for the presence of "low muscle mass" (mid-arm muscle circumferencelow muscle mass. In patients with and without low muscle mass, severity of liver disease and characteristics of infections were similar. Mortality tended to be higher in patients with low muscle mass (47% vs 26%, P = .06). A multivariate analysis selected low muscle mass (P low muscle mass compared with those without (50% vs 16%; P = .01). The mortality rate and the incidence of complications in malnourished patients classified in Child-Pugh A-B were similar to those Child-Pugh C. Low muscle mass worsen prognosis in cirrhotic patients with severe infections. This is particularly evident in patients with Child A-B cirrhosis in whom the coexistence of low muscle mass and sepsis caused a negative impact on mortality similar to that observable in all Child C patients with sepsis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Alfacalcidol improves muscle power, muscle function and balance in elderly patients with reduced bone mass.

    Science.gov (United States)

    Schacht, E; Ringe, Johann D

    2012-01-01

    We investigated the effect of daily therapy with 1 mcg alfacalcidol (Doss(®)-TEVA/AWD-pharma) on muscle power, muscle function, balance performance and fear of falls in an open, multi-centered, uncontrolled, prospective study on a cohort of patients with reduced bone mass. Among the 2,097 participants, 87.1% were post-menopausal women and 12.9% were men. Mean age was 74.8 years and mean body mass index (BMI) 26.3 kg/m². A total of 75.3% of the study population had osteoporosis, 81% a diagnosis of "increased risk of falls" and 70.1% had a creatinine clearance (CrCl) of power tests at onset and after 3 and 6 months: the timed up and go test (TUG) and the chair rising test (CRT). At baseline and after 6 months, participants performed the tandem gait test (TGT) and filled out a questionnaire evaluating fear of falling. Successful performance in the muscle tests is associated with a significantly lower risk of falls and non-vertebral fractures in elderly patients (successful test performance: TUG ≤ 10 s (sec), CRT ≤ 10 s, TGT ≥ 8 steps). A significant improvement in the performance of the two muscle tests was proved already after 3 months of treatment with alfacalcidol and further increased by the end of the therapeutic intervention. There were significant increases in the number of participants able to successfully perform the tests: 24.6% at baseline and 46.3% at the end of trial for the TUG (P balance test (TGT) increased from 36.0% at onset to 58.6% at the end of the trial (P power, muscle function and balance and reduces fear of falls. The significant improvement in the three muscle and balance tests and fear of falls may have a preventative effect on falls and fractures. We suggest that the quantitative risk tests used in this study could be reliable surrogate parameters for the risk of falls and fractures in elderly patients.

  6. Relationship between oxidative stress and muscle mass loss in early postmenopause: an exploratory study.

    Science.gov (United States)

    Zacarías-Flores, Mariano; Sánchez-Rodríguez, Martha A; García-Anaya, Oswaldo Daniel; Correa-Muñoz, Elsa; Mendoza-Núñez, Víctor Manuel

    2018-04-09

    Endocrine changes due to menopause have been associated to oxidative stress and muscle mass loss. The study objective was to determine the relationship between both variables in early postmenopause. An exploratory, cross-sectional study was conducted in 107 pre- and postmenopausal women (aged 40-57 years). Levels of serum lipid peroxides and uric acid and enzymes superoxide dismutase and glutathione peroxidase, as well as total plasma antioxidant capacity were measured as oxidative stress markers. Muscle mass using bioelectrical impedance and muscle strength using dynamometry were also measured. Muscle mass, skeletal muscle index, fat-free mass, and body mass index were calculated. More than 90% of participants were diagnosed with overweight or obesity. Postmenopausal women had lower values of muscle mass and strength markers, with a negative correlation between lipid peroxide level and skeletal muscle index (r= -0.326, p<.05), and a positive correlation between uric acid and skeletal muscle index (r=0.295, p<.05). A multivariate model including oxidative stress markers, age, and waist circumference showed lipid peroxide level to be the main contributor to explain the decrease in skeletal muscle mass in postmenopause, since for every 0.1μmol/l increase in lipid peroxide level, skeletal muscle index decreases by 3.03 units. Our findings suggest an association between increased oxidative stress and muscle mass loss in early postmenopause. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. The effect Mat Pilates practice on muscle mass in elderly women

    Directory of Open Access Journals (Sweden)

    Leliz Cristina Sampaio Queiroz

    2016-01-01

    Full Text Available Objective: to verify that the Mat Pilates practice increases muscle mass in elderly women. Methods: quasi-experimental study with primary data collection and with a convenience sample. The muscle mass of 43 elderly was evaluated for 11 weeks, by calculating the arm muscle area, before and after the intervention. Results:statistically significant difference was observed (p<0.002 between the average value of the arm muscle area, before (35.56cm2 and after the exercises (42.72cm2. Conclusion: mat Pilates program generates positive effect on increasing the muscle mass of elderly.

  8. Creatine Loading Does Not Preserve Muscle Mass or Strength During Leg Immobilization in Healthy, Young Males

    NARCIS (Netherlands)

    Backx, Evelien M.P.; Hangelbroek, Roland; Snijders, Tim; Verscheijden, Marie Louise; Verdijk, Lex B.; Groot, de Lisette C.P.G.M.; Loon, van Luc J.C.

    2017-01-01

    Background: A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise

  9. Heterokaryon analysis of muscle differentiation: regulation of the postmitotic state.

    Science.gov (United States)

    Clegg, C H; Hauschka, S D

    1987-08-01

    MM14 mouse myoblasts withdraw irreversibly from the cell cycle and become postmitotic within a few hours of being deprived of fibroblast growth factor (Clegg, C. H., T. A. Linkhart, B. B. Olwin, and S. D. Hauschka, 1987, J. Cell Biol., 105:949-956). To examine the mechanisms that may regulate this developmental state of skeletal muscle, we tested the mitogen responsiveness of various cell types after their polyethylene glycol-mediated fusion with post-mitotic myocytes. Heterokaryons containing myocytes and quiescent nonmyogenic cells such as 3T3, L cell, and a differentiation-defective myoblast line (DD-1) responded to mitogen-rich medium by initiating DNA synthesis. Myonuclei replicated DNA and reexpressed thymidine kinase. In contrast, (myocyte x G1 myoblast) heterokaryons failed to replicate DNA in mitogen-rich medium and became postmitotic. This included cells with a nuclear ratio of three myoblasts to one myocyte. Proliferation dominance in (myocyte x 3T3 cell) and (myocyte x DD-1) heterokaryons was conditionally regulated by the timing of mitogen treatment; such cells became postmitotic when mitogen exposure was delayed for as little as 6 h after cell fusion. In addition, (myocyte x DD-1) heterokaryons expressed a muscle-specific trait and lost epidermal growth factor receptors when they became postmitotic. These results demonstrate that DNA synthesis is not irreversibly blocked in skeletal muscle; myonuclei readily express proliferation-related functions when provided with a mitogenic signal. Rather, myocyte-specific repression of DNA synthesis in heterokaryons argues that the postmitotic state of skeletal muscle is regulated by diffusible factors that inhibit processes of cellular mitogenesis.

  10. Legal regulations for handling mass proceedings

    International Nuclear Information System (INIS)

    Kopp, F.

    1980-01-01

    The author explains legal regulations to be found in administrative law and in the drafted version of rules of administrative procedures on the calling-in of third parties, on common attorneys, on the publication of service etc. and on other simplifications of proceedings with the aim to make mass proceedings administerable. As a result, the author considers these special regulations to be largely dispensable and risky with regard to constitutional law. An extension of constitutional guarantees pertaining to administrative procedures is necessary in order not to overburden Courts by tasks which may be fulfilled in a better way by federal agencies. The solution is to be found in substantive law: if necessary by admitting the so-called participation of associations or, even better, by introducing an agent safeguarding public interests in administrative procedures. (HSCH) [de

  11. PGC-1α regulates alanine metabolism in muscle cells.

    Science.gov (United States)

    Hatazawa, Yukino; Qian, Kun; Gong, Da-Wei; Kamei, Yasutomi

    2018-01-01

    The skeletal muscle is the largest organ in the human body, depositing energy as protein/amino acids, which are degraded in catabolic conditions such as fasting. Alanine is synthesized and secreted from the skeletal muscle that is used as substrates of gluconeogenesis in the liver. During fasting, the expression of PGC-1α, a transcriptional coactivator of nuclear receptors, is increased in the liver and regulates gluconeogenesis. In the present study, we observed increased mRNA expression of PGC-1α and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting. In C2C12 myoblast cells overexpressing PGC-1α, ALT2 expression was increased concomitant with an increased alanine level in the cells and medium. In addition, PGC-1α, along with nuclear receptor ERR, dose-dependently enhanced the ALT2 promoter activity in reporter assay using C2C12 cells. In the absence of glucose in the culture medium, mRNA levels of PGC-1α and ALT2 increased. Endogenous PGC-1α knockdown in C2C12 cells reduced ALT2 gene expression level, induced by the no-glucose medium. Taken together, in the skeletal muscle, PGC-1α activates ALT2 gene expression, and alanine production may play roles in adaptation to fasting.

  12. Correlation between Body Mass Index, Gender, and Skeletal Muscle Mass Cut off Point in Bandung

    Directory of Open Access Journals (Sweden)

    Richi Hendrik Wattimena

    2017-09-01

    Full Text Available Objective: To determine the average skeletal muscle mass (SMM value in young adults as a reference population; to analyze the correlation of gender, and body mass index to the cut off point; and to determine skeletal muscle mass cut off points of population in Bandung, Indonesia. Methods: This was a cross-sectional study involving 199 participants, 122 females and 77 males. The sampling technique used was the multistage random sampling. The participants were those who lived in four major regions in Bandung, Indonesia: Sukajadi, Cicadas, Buah Batu, and Cibaduyut. Results: The average appendicular skeletal mass index (ASMI in females and males based on body mass index (BMI were identified. The average ASMI values for normal BMI in females was 5.982±0.462 kg/m2 while the average ASMI values normal BMI for males was 7.581±0.744 kg/m2 Conclusions: A correlation between BMI and ASMI that was considered statistically significant was found in females (0.7712; p<0.05 and a very significant correlation was seen in males (0.870; p<0.05. The cut off points were defined by the normal BMI, which were 5.059 for females and 6.093 for males.

  13. Genes Whose Gain or Loss-Of-Function Increases Skeletal Muscle Mass in Mice: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Sander A. J. Verbrugge

    2018-05-01

    Full Text Available Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform, Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a Igf1-Akt-mTOR pathway, (b myostatin-Smad signaling, and (c the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.

  14. A New Equation to Estimate Muscle Mass from Creatinine and Cystatin C.

    Directory of Open Access Journals (Sweden)

    Sun-wook Kim

    Full Text Available With evaluation for physical performance, measuring muscle mass is an important step in detecting sarcopenia. However, there are no methods to estimate muscle mass from blood sampling.To develop a new equation to estimate total-body muscle mass with serum creatinine and cystatin C level, we designed a cross-sectional study with separate derivation and validation cohorts. Total body muscle mass and fat mass were measured using dual-energy x-ray absorptiometry (DXA in 214 adults aged 25 to 84 years who underwent physical checkups from 2010 to 2013 in a single tertiary hospital. Serum creatinine and cystatin C levels were also examined.Serum creatinine was correlated with muscle mass (P < .001, and serum cystatin C was correlated with body fat mass (P < .001 after adjusting glomerular filtration rate (GFR. After eliminating GFR, an equation to estimate total-body muscle mass was generated and coefficients were calculated in the derivation cohort. There was an agreement between muscle mass calculated by the novel equation and measured by DXA in both the derivation and validation cohort (P < .001, adjusted R2 = 0.829, β = 0.95, P < .001, adjusted R2 = 0.856, β = 1.03, respectively.The new equation based on serum creatinine and cystatin C levels can be used to estimate total-body muscle mass.

  15. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation

    DEFF Research Database (Denmark)

    Dzamko, Nicolas; Schertzer, Jonathan D.; Ryall, James G.

    2008-01-01

    The activation of AMP-activated protein kinase (AMPK) and phosphorylation/inhibition of acetyl-CoA carboxylase 2 (ACC2) is believed to be the principal pathway regulating fatty acid oxidation. However, during exercise AMPK activity and ACC Ser-221 phosphorylation does not always correlate...... with rates of fatty acid oxidation. To address this issue we have investigated the requirement for skeletal muscle AMPK in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) and contraction-stimulated fatty acid oxidation utilizing transgenic mice expressing a muscle-specific kinase...... dead (KD) AMPK alpha2. In wild-type (WT) mice, AICAR and contraction increased AMPK alpha2 and alpha1 activities, the phosphorylation of ACC2 and rates of fatty acid oxidation while tending to reduce malonyl-CoA levels. Despite no activation of AMPK in KD mice, ACC2 phosphorylation was maintained...

  16. Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis.

    Science.gov (United States)

    Findeisen, Hannes M; Kahles, Florian K; Bruemmer, Dennis

    2013-04-01

    Epigenetics involve heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Epigenetic mechanisms constitute a hierarchic upper-level of transcriptional control through complex modifications of chromosomal components and nuclear structures. These modifications include, for example, DNA methylation or post-translational modifications of core histones; they are mediated by various chromatin-modifying enzymes; and ultimately they define the accessibility of a transcriptional complex to its target DNA. Integrating epigenetic mechanisms into the pathophysiologic concept of complex and multifactorial diseases such as atherosclerosis may significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches. Although still in its infancy, intriguing scientific progress has begun to elucidate the role of epigenetic mechanisms in vascular biology, particularly in the control of smooth muscle cell phenotypes. In this review, we will summarize epigenetic pathways in smooth muscle cells, focusing on mechanisms involved in the regulation of vascular remodeling.

  17. Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department.

    Science.gov (United States)

    Lee, YoonJe; Park, Hyun Kyung; Kim, Won Young; Kim, Myung Chun; Jung, Woong; Ko, Byuk Sung

    2018-05-08

    Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed. © 2018 S. Karger AG, Basel.

  18. Relationships of 35 lower limb muscles to height and body mass quantified using MRI.

    Science.gov (United States)

    Handsfield, Geoffrey G; Meyer, Craig H; Hart, Joseph M; Abel, Mark F; Blemker, Silvia S

    2014-02-07

    Skeletal muscle is the most abundant tissue in the body and serves various physiological functions including the generation of movement and support. Whole body motor function requires adequate quantity, geometry, and distribution of muscle. This raises the question: how do muscles scale with subject size in order to achieve similar function across humans? While much of the current knowledge of human muscle architecture is based on cadaver dissection, modern medical imaging avoids limitations of old age, poor health, and limited subject pool, allowing for muscle architecture data to be obtained in vivo from healthy subjects ranging in size. The purpose of this study was to use novel fast-acquisition MRI to quantify volumes and lengths of 35 major lower limb muscles in 24 young, healthy subjects and to determine if muscle size correlates with bone geometry and subject parameters of mass and height. It was found that total lower limb muscle volume scales with mass (R(2)=0.85) and with the height-mass product (R(2)=0.92). Furthermore, individual muscle volumes scale with total muscle volume (median R(2)=0.66), with the height-mass product (median R(2)=0.61), and with mass (median R(2)=0.52). Muscle volume scales with bone volume (R(2)=0.75), and muscle length relative to bone length is conserved (median s.d.=2.1% of limb length). These relationships allow for an arbitrary subject's individual muscle volumes to be estimated from mass or mass and height while muscle lengths may be estimated from limb length. The dataset presented here can further be used as a normative standard to compare populations with musculoskeletal pathologies. © 2013 Published by Elsevier Ltd.

  19. Synemin acts as a regulator of signalling molecules during skeletal muscle hypertrophy.

    Science.gov (United States)

    Li, Zhenlin; Parlakian, Ara; Coletti, Dario; Alonso-Martin, Sonia; Hourdé, Christophe; Joanne, Pierre; Gao-Li, Jacqueline; Blanc, Jocelyne; Ferry, Arnaud; Paulin, Denise; Xue, Zhigang; Agbulut, Onnik

    2014-11-01

    Synemin, a type IV intermediate filament (IF) protein, forms a bridge between IFs and cellular membranes. As an A-kinase-anchoring protein, it also provides temporal and spatial targeting of protein kinase A (PKA). However, little is known about its functional roles in either process. To better understand its functions in muscle tissue, we generated synemin-deficient (Synm(-) (/-)) mice. Synm(-) (/-) mice displayed normal development and fertility but showed a mild degeneration and regeneration phenotype in myofibres and defects in sarcolemma membranes. Following mechanical overload, Synm(-) (/-) mice muscles showed a higher hypertrophic capacity with increased maximal force and fatigue resistance compared with control mice. At the molecular level, increased remodelling capacity was accompanied by decreased myostatin (also known as GDF8) and atrogin (also known as FBXO32) expression, and increased follistatin expression. Furthermore, the activity of muscle-mass control molecules (the PKA RIIα subunit, p70S6K and CREB1) was increased in mutant mice. Finally, analysis of muscle satellite cell behaviour suggested that the absence of synemin could affect the balance between self-renewal and differentiation of these cells. Taken together, our results show that synemin is necessary to maintain membrane integrity and regulates signalling molecules during muscle hypertrophy. © 2014. Published by The Company of Biologists Ltd.

  20. mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Parker, Benjamin L; Chaudhuri, Rima

    2016-01-01

    culture. RESULTS: Ric mKO mice exhibited a greater reliance on fat as an energy substrate, a re-partitioning of lean to fat mass and an increase in intramyocellular triglyceride (IMTG) content, along with increases in several lipid metabolites in muscle. Unbiased proteomics revealed an increase......OBJECTIVE: We have recently shown that acute inhibition of both mTOR complexes (mTORC1 and mTORC2) increases whole-body lipid utilization, while mTORC1 inhibition had no effect. Therefore, we tested the hypothesis that mTORC2 regulates lipid metabolism in skeletal muscle. METHODS: Body composition...... in the expression of the lipid droplet binding protein Perilipin 3 (PLIN3) in muscle from Ric mKO mice. This was associated with increased AMPK activity in Ric mKO muscle. Reducing AMPK kinase activity decreased muscle PLIN3 expression and IMTG content. AMPK agonism, in turn, increased PLIN3 expression in a FoxO1...

  1. Non-Hodgkin lymphoma in skeletal muscle manifesting as homogeneous masses with CT attenuation similar to muscle

    International Nuclear Information System (INIS)

    Panicek, D.M.; Lautin, J.L.; Schwartz, L.H.; Castellino, R.A.

    1997-01-01

    Two cases are presented of masses in muscle due to non-Hodgkin lymphoma (NHL) that were homogeneous and isoattenuating to normal muscle on CT. In each case, the mass was clinically suspected of representing soft tissue sarcoma. However, the masses were relatively inapparent on CT, being visible predominantly as mass effect - an appearance unlike that of soft tissue sarcomas. It is important to be aware that NHL in muscle can be difficult to detect at CT, even with intravenous contrast enhancement; therefore, a clinically apparent mass should not be dismissed on the basis of an apparently unremarkable CT scan of the region. Such findings should suggest the diagnosis of NHL rather than sarcoma. (orig.)

  2. Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Jensen, Thomas Elbenhardt; Kleinert, Maximilian

    2013-01-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates...

  3. Imaging mass spectrometry reveals fiber-specific distribution of acetylcarnitine and contraction-induced carnitine dynamics in rat skeletal muscles.

    Science.gov (United States)

    Furuichi, Yasuro; Goto-Inoue, Naoko; Manabe, Yasuko; Setou, Mitsutoshi; Masuda, Kazumi; Fujii, Nobuharu L

    2014-10-01

    Carnitine is well recognized as a key regulator of long-chain fatty acyl group translocation into the mitochondria. In addition, carnitine, as acetylcarnitine, acts as an acceptor of excess acetyl-CoA, a potent inhibitor of pyruvate dehydrogenase. Here, we provide a new methodology for accurate quantification of acetylcarnitine content and determination of its localization in skeletal muscles. We used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to visualize acetylcarnitine distribution in rat skeletal muscles. MALDI-IMS and immunohistochemistry of serial cross-sections showed that acetylcarnitine was enriched in the slow-type muscle fibers. The concentration of ATP was lower in muscle regions with abundant acetylcarnitine, suggesting a relationship between acetylcarnitine and metabolic activity. Using our novel method, we detected an increase in acetylcarnitine content after muscle contraction. Importantly, this increase was not detected using traditional biochemical assays of homogenized muscles. We also demonstrated that acetylation of carnitine during muscle contraction was concomitant with glycogen depletion. Our methodology would be useful for the quantification of acetylcarnitine and its contraction-induced kinetics in skeletal muscles. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Vitamin D prevents lipid accumulation in murine muscle through regulation of PPARγ and perilipin-2 expression.

    Science.gov (United States)

    Li, Jiarong; Mihalcioiu, Milton; Li, Lifeng; Zakikhani, Mahvash; Camirand, Anne; Kremer, Richard

    2018-03-01

    Vitamin D plays an important role in regulation of skeletal muscle tone and contraction. Serum vitamin D status is linked to muscle power and force in adolescent girls, and vitamin D deficiency is associated with myopathies in children and poorer physical performance in the elderly. We previously reported that vitamin D deficiency is linked to a significant increase in muscle fatty infiltration in healthy young women, and studies in patients with neuromuscular disorders also associate muscle weakening and lipid content. In order to better understand the link between vitamin D status and skeletal muscle lipid metabolism, we compared the effect of a low (25IU/kg) or normal (1000IU/kg) vitamin D 3 diet on muscle fat in female FVB mice maintained in a room without UVB lighting to minimize endogenous vitamin D production. Animals on low vitamin D diet displayed lower circulating 25(OH)D levels and a dramatic increase (287±52% compared to normal diet, p<0.0001) in lipid deposition in skeletal muscle accompanied by muscle fiber disorganization. Lipid droplet staining increased by 242±23% (p<0.0001) in low vitamin D diet, and lipid droplet coat protein perilipin-2 and nuclear receptor transcription factor PPARγ expression levels were increased compared to mice fed the normal vitamin D diet: average staining for PLIN2: 0.22±0.08 (25IU/kg diet) vs 0.10±0.02 (1000IU/kg). Average staining for PPARγ: 0.24±0.06 (25IU/kg diet) vs 0.07±0.04 (1000IU/kg) p<0.0001. Tissue mass spectrometry imaging revealed major differences in muscle phospholipids profile depending on diet. In vitro, 1,25(OH) 2 D 3 treatment of 3T3-L1 pre-adipocytes inhibited appearance of lipid droplets by 79±9.3%, and caused a 80±10% and 25±8% (p=0.001) reduction in PPARγ and perilipin-2 mRNA levels (by qPCR) compared to control cells. In summary, we report here the first in vivo model illustrating the important structural muscle fiber disorganization and fat accumulation inside and outside muscle

  5. Comparison of skeletal muscle mass to fat-free mass ratios among different ethnic groups.

    Science.gov (United States)

    Abe, T; Bemben, M G; Kondo, M; Kawakami, Y; Fukunaga, T

    2012-01-01

    Asians seem to have less skeletal muscle mass (SMM) than other ethnic groups, but it is not clear whether relative SMM, i.e., SMM / height square or SMM to fat-free mass (FFM) ratio, differs among different ethnic groups at the same level of body mass index (BMI). To compare the SMM to fat-free mass (FFM) ratio as well as anthropometric variables and body composition among 3 ethnic groups. Three hundred thirty-nine Japanese, 343 Brazilian, and 183 German men and women were recruited for this cross-sectional study. Muscle thickness (MTH) and subcutaneous fat thickness (FTH) were measured by ultrasound at nine sites on the anterior and posterior aspects of the body. FTH was used to estimate the body density, from which fat mass and fat-free mass (FFM) was calculated by using Brozek equation. Total SMM was estimated from ultrasound-derived prediction equations. Percentage body fat was similar among the ethnic groups in men, while Brazilians were higher than Japanese in women. In German men and women, absolute SMM and FFM were higher than in their Japanese and Brazilians counterparts. SMM index and SMM:FFM ratios were similar among the ethnic groups in women, excluding SMM:FFM ratio in Brazilian. In men, however, these relative values (SMM index and SMM:FFM ratio) were still higher in Germans. After adjusting for age and BMI, the SMM index and SMM:FFM ratios were lower in Brazilian men and women compared with the other two ethnic groups, while the SMM index and SMM:FFM ratios were similar in Japanese and German men and women, excluding SMM:FFM ratio in women. Our results suggest that relative SMM is not lower in Asian populations compared with European populations after adjusted by age and BMI.

  6. Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

    Science.gov (United States)

    Farshidfar, Farnaz; Pinder, Mark A; Myrie, Semone B

    2017-01-01

    Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Thyroid hormones regulate skeletal muscle regeneration after acute injury.

    Science.gov (United States)

    Leal, Anna Lúcia R C; Albuquerque, João Paulo C; Matos, Marina S; Fortunato, Rodrigo S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia Maria Corrêa

    2015-02-01

    We evaluated the effects of hypo- and hyperthyroid statuses during the initial phase of skeletal muscle regeneration in rats. To induce hypo- or hyperthyroidism, adult male Wistar rats were treated with methimazole (0.03%) or T4 (10 μg/100 g), respectively, for 10 days. Three days before sacrifice, a crush injury was produced in the solear muscles of one half of the animals, while the other half remained intact. T3, T4, TSH, and leptin serum levels were not affected by the injury. Serum T3 and T4 levels were significantly increased in hyperthyroid and hyper-injury animals. Hypothyroidism was confirmed by the significant increase in serum TSH levels in hypothyroid and hypo-injury animals. Injury increased cell infiltration and macrophage accumulation especially in hyperthyroid animals. Both type 2 and type 3 deiodinases were induced by lesion, and the opposite occurred with the type 1 isoform, at least in the control and hyperthyroid groups. Injury increased both MyoD and myogenin expression in all the studied groups, but only MyoD expression was increased by thyroidal status only at the protein level. We conclude that thyroid hormones modulate skeletal muscle regeneration possibly by regulating the inflammatory process, as well as MyoD and myogenin expression in the injured tissue.

  8. Bio-impedance analysis for appendicular skeletal muscle mass assessment in (pre-) frail elderly people

    NARCIS (Netherlands)

    Baar, van H.; Hulshof, P.J.M.; Tieland, C.A.B.; Groot, de C.P.G.M.

    2015-01-01

    Background & aims Screening populations for skeletal muscle mass (SMM) is important for early detection of sarcopenia. Our aim was to develop an age specific bio-impedance (BI) prediction equation for the assessment of appendicular skeletal muscle mass (ASMM) in (pre-) frail elderly people aged

  9. Abelson tyrosine-protein kinase 2 regulates myoblast proliferation and controls muscle fiber length

    OpenAIRE

    Lee, Jennifer K; Hallock, Peter T; Burden, Steven J

    2017-01-01

    Muscle fiber length is nearly uniform within a muscle but widely different among different muscles. We show that Abelson tyrosine-protein kinase 2 (Abl2) has a key role in regulating myofiber length, as a loss of Abl2 leads to excessively long myofibers in the diaphragm, intercostal and levator auris muscles but not limb muscles. Increased myofiber length is caused by enhanced myoblast proliferation, expanding the pool of myoblasts and leading to increased myoblast fusion. Abl2 acts in myobla...

  10. Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice

    National Research Council Canada - National Science Library

    Zimmers, Teresa

    2006-01-01

    .... Mice lacking the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin Receptor Type IIB, display heightened muscle mass...

  11. Regulation of myostatin expression is associated with growth and muscle development in commercial broiler and DMC muscle

    NARCIS (Netherlands)

    Dou, Tengfei; Li, Zhengtian; Wang, Kun; Liu, Lixian; Rong, Hua; Xu, Zhiqiang; Huang, Ying; Gu, Dahai; Chen, Xiaobo; Hu, Wenyuan; Zhang, Jiarong; Zhao, Sumei; Jois, Markandeya; Li, Qihua; Ge, Changrong; Pas, te Marinus F.W.; Jia, Junjing

    2018-01-01

    Myostatin is a negative regulator of skeletal muscle growth. Muscle tissue is the largest tissue in the body and influences body growth. Commercial Avian broiler chickens are selected for high growth rate and muscularity. Daweishan mini chickens are a slow growing small-sized chicken breed. We

  12. Relationship of Muscle Mass Determined by DEXA with Spirometric Results in Healthy Individuals.

    Science.gov (United States)

    Martín Holguera, Rafael; Turrión Nieves, Ana Isabel; Rodríguez Torres, Rosa; Alonso, María Concepción

    2017-07-01

    Muscle mass maybe a determining factor in the variability of spirometry results in individuals of the same sex and age who have similar anthropometric characteristics. The aim of this study was to determine the association between spirometric results from healthy individuals and their muscle mass assessed by dual energy X-ray absorptiometry (DEXA). A sample of 161 women and 144 men, all healthy non-smokers, was studied. Ages ranged from18 to77years. For each subject, spirometry results and total and regional lean mass values obtained by full body DEXA were recorded. A descriptive analysis of the variables and a regression analysis were performed to study the relationship between spirometric variables and lean body mass, correcting for age and body mass index (BMI). In both sexes all muscle mass variables correlated positively and significantly with spirometric variables, and to a greater extent in men. After partial adjustment of correlations by age and BMI, the factor which best explains the spirometric variables is the total lean body mass in men, and trunk lean body mass in women. In men, muscle mass in the lower extremities is most closely associated with spirometric results. In women, it is the muscle mass of the trunk. In both sexes muscle mass mainly affects FEV 1 . Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Richter, Erik; Wojtaszewski, Jørgen

    2006-01-01

    The 5'-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism...... during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We...... in relation to adaptation of skeletal muscle to exercise training....

  14. Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia

    Science.gov (United States)

    Kim, Kyoung Min; Jang, Hak Chul; Lim, Soo

    2016-01-01

    Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective. PMID:27334763

  15. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; Nyengaard, J R

    2014-01-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind...... of periosteal BFR/BS (2-fold increase vs. BTX, Pmuscle mass (+29% vs. BTX, Pmuscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse......BMD, -13%, Pmuscle mass (-69%, Pmuscle cell cross sectional area (CSA) (-73%, P

  16. High risk of malnutrition is associated with low muscle mass in older hospitalized patients - a prospective cohort study.

    Science.gov (United States)

    Pierik, Vincent D; Meskers, Carel G M; Van Ancum, Jeanine M; Numans, Siger T; Verlaan, Sjors; Scheerman, Kira; Kruizinga, Roeliene C; Maier, Andrea B

    2017-06-05

    Malnutrition, low muscle strength and muscle mass are highly prevalent in older hospitalized patients and associated with adverse outcomes. Malnutrition may be a risk factor for developing low muscle mass. We aimed to investigate the association between the risk of malnutrition and 1) muscle strength and muscle mass at admission and 2) the change of muscle strength and muscle mass during hospitalization in older patients. The EMPOWER study included 378 patients aged seventy years or older who were acutely or electively admitted to four different wards of an academic teaching hospital in Amsterdam. Patients were grouped into low risk of malnutrition and high risk of malnutrition based on the Short Nutritional Assessment Questionnaire (SNAQ) score and were assessed for hand grip strength and muscle mass using hand held dynamometry respectively bioelectrical impedance analysis (BIA) within 48 h after admission and at day seven, or earlier at the day of discharge. Muscle mass was expressed as skeletal muscle mass, appendicular lean mass, fat free mass and the skeletal muscle index. The mean age of the patients was 79.7 years (SD 6.39), 48.9% were female. At admission, being at high risk of malnutrition was significantly associated with lower muscle mass (Odds Ratio, 95% CI, 0.90, 0.85-0.96), but not with muscle strength. Muscle strength and muscle mass did not change significantly during hospitalization in both groups. In older hospitalized patients, a high risk of malnutrition is associated with lower muscle mass at admission, but not with muscle strength nor with change of either muscle strength or muscle mass during hospitalization.

  17. Subclinical hypothyroidism has little influences on muscle mass or strength in elderly people.

    Science.gov (United States)

    Moon, Min Kyong; Lee, You Jin; Choi, Sung Hee; Lim, Soo; Yang, Eun Joo; Lim, Jae-Young; Paik, Nam-Jong; Kim, Ki Woong; Park, Kyong Soo; Jang, Hak C; Cho, Bo Youn; Park, Young Joo

    2010-08-01

    Sarcopenia, the age-related decline in muscle mass, affects the muscle strength and muscle quality, and these changes decrease functional capacity. The prevalence of thyroid dysfunction increases with age, and changes in thyroid hormone level lead to neuromuscular deficits. We investigated the effects of subclinical hypothyroidism on the muscle mass, strength or quality in elderly people. One thousand one hundred eighteen subjects aged > or = 65 yr were randomly selected from a local population and classified into a euthyroid (280 men and 358 women), subclinically hypothyroid (61 men and 75 women), or overtly hypothyroid (7 men and 16 women) group. Although women with subclinical hypothyroidism had a higher prevalence of sarcopenia, defined according to the ratio of appendicular skeletal muscle mass to the square of height, muscle mass, strength or quality did not differ in relation to thyroid status in men or in women. Multivariate analysis including age, diabetes, hypertension, acute coronary event, alcohol, smoking, presence of pain, physical activity score, and lipid profile, showed that thyroid-stimulating hormone level was not associated with muscle mass, strength or quality. In conclusion, subclinical hypothyroidism has little influences on muscle mass, strength or quality, and may not be associated with sarcopenia.

  18. Improved skeletal muscle mass and strength after heavy strength training in very old individuals

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus Leidesdorff; Malmgaard-Clausen, Nikolaj Mølkjær; Gliese, Bjørn

    2017-01-01

    , muscle fiber type distribution and size did not differ significantly between groups. We conclude that in protein supplemented very old individuals, heavy resistance training can increase muscle mass and strength, and that the relative improvement in mass is more pronounced when initial muscle mass is low.......Age-related loss of muscle mass and function represents personal and socioeconomic challenges. The purpose of this study was to determine the adaptation of skeletal musculature in very old individuals (83 + years) performing 12 weeks of heavy resistance training (3 ×/week) (HRT) compared to a non....... The increase in CSA is correlated inversely with the baseline level of CSA (R2 = 0.43, P muscle isometric strength, isokinetic peak torque and power increased significantly only in HRT by 10–15%, whereas knee extension one-repetition maximum (1 RM) improved by 91%. Physical functional tests...

  19. Phenotype selection reveals coevolution of muscle glycogen and protein and PTEN as a gate keeper for the accretion of muscle mass in adult female mice.

    Directory of Open Access Journals (Sweden)

    Mandy Sawitzky

    Full Text Available We have investigated molecular mechanisms for muscle mass accretion in a non-inbred mouse model (DU6P mice characterized by extreme muscle mass. This extreme muscle mass was developed during 138 generations of phenotype selection for high protein content. Due to the repeated trait selection a complex setting of different mechanisms was expected to be enriched during the selection experiment. In muscle from 29-week female DU6P mice we have identified robust increases of protein kinase B activation (AKT, Ser-473, up to 2-fold if compared to 11- and 54-week DU6P mice or controls. While a number of accepted effectors of AKT activation, including IGF-I, IGF-II, insulin/IGF-receptor, myostatin or integrin-linked kinase (ILK, were not correlated with this increase, phosphatase and tensin homologue deleted on chromosome 10 (PTEN was down-regulated in 29-week female DU6P mice. In addition, higher levels of PTEN phosphorylation were found identifying a second mechanism of PTEN inhibition. Inhibition of PTEN and activation of AKT correlated with specific activation of p70S6 kinase and ribosomal protein S6, reduced phosphorylation of eukaryotic initiation factor 2α (eIF2α and higher rates of protein synthesis in 29-week female DU6P mice. On the other hand, AKT activation also translated into specific inactivation of glycogen synthase kinase 3ß (GSK3ß and an increase of muscular glycogen. In muscles from 29-week female DU6P mice a significant increase of protein/DNA was identified, which was not due to a reduction of protein breakdown or to specific increases of translation initiation. Instead our data support the conclusion that a higher rate of protein translation is contributing to the higher muscle mass in mid-aged female DU6P mice. Our results further reveal coevolution of high protein and high glycogen content during the selection experiment and identify PTEN as gate keeper for muscle mass in mid-aged female DU6P mice.

  20. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle...

  1. Redox regulation of calcium release in skeletal and cardiac muscle

    Directory of Open Access Journals (Sweden)

    CECILIA HIDALGO

    2002-01-01

    Full Text Available In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist and Mg2+ (endogenous inhibitor on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 µM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 µM [Ca2+]. In 10 µM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] ­ 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 µM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed

  2. Relation between body mass index percentile and muscle strength ...

    African Journals Online (AJOL)

    Noha Abdel Kader Abdel Kader Hasan

    2016-02-01

    Feb 1, 2016 ... Abstract Background: Muscle strength and endurance in children are very important to develop physical .... the Faculty of Physical Therapy, Cairo university, was used to ..... [9] Noelle G. Quantification of muscle fatigue in cerebral palsy and ... Bouckaert J. Physical fitness and physical activity in obese and.

  3. Association between healthy diet and exercise and greater muscle mass in older adults.

    Science.gov (United States)

    Kim, Jinhee; Lee, Yunhwan; Kye, Seunghee; Chung, Yoon-Sok; Kim, Kwang-Min

    2015-05-01

    To examine the association between healthy diet and exercise, individually and combined, and low muscle mass in older Korean adults. Population-based cross-sectional study from the Fourth and Fifth Korea National Health and Nutrition Examination Surveys from 2008 to 2011. Community. Nationally representative sample aged 65 and older (1,486 men, 1,799 women) in the Republic of Korea. A food frequency questionnaire was used to determine frequency of food group consumption (meat, fish, eggs, legumes; vegetables; fruits). Participation in exercise (aerobic and resistance) was based on self-report. Combined healthy lifestyle factors were calculated as the number of recommendations met regarding consumption of food groups and exercise performed. Appendicular skeletal muscle mass (ASM) was measured using dual-energy X-ray absorptiometry, and low muscle mass was defined using the variable of ASM adjusted for weight. Logistic regression analysis was performed to examine the association between healthy lifestyle factors and low muscle mass, adjusting for sociodemographic characteristics and health-related variables. In women, after controlling for covariates, vegetable consumption (odds ratio (OR)=0.52, 95% confidence interval (CI)=0.30-0.89) and aerobic exercise (OR=0.62, 95% CI=0.39-1.00) were inversely associated with low muscle mass. Also, the odds of low muscle mass was lower in women with three or more healthy lifestyle factors versus none (OR=0.45, 95% CI=0.23-0.87). In men, there were no associations between food group consumption and exercise and low muscle mass. Older women who exercise and consume a healthy diet have lower odds of low muscle mass. Engaging in multiple healthy behaviors may be important in preventing low muscle mass in late life. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  4. Decreased muscle mass in Korean subjects with intracranial arterial stenosis: The Kangbuk Samsung Health Study.

    Science.gov (United States)

    Jung, Ho-Jung; Jung, Hwanseok; Lee, Taeyoung; Kim, Jongho; Park, Jongsin; Kim, Hacsoo; Cho, Junghwan; Lee, Won-Young; Park, Sung-Woo; Rhee, Eun-Jung; Oh, Hyung-Geun

    2017-01-01

    Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians. Decreased muscle mass is one of the major causes of chronic disease in adults. The purpose of this study was to analyze the relationship between muscle mass and ICAS in Korean adults. For this study, we selected a total of 10,530 participants (mean age, 43.3 years; 8558 men) in a health screening program, for whom transcranial Doppler (TCD) ultrasound was used to detect >50% ICAS based on criteria modified from the stroke outcomes and neuroimaging of intracranial atherosclerosis trial. Body composition was evaluated by bioelectrical impedance analysis (BIA). Skeletal muscle index (SMI) was calculated with muscle mass/weight (kg) * 100. Among the total patient population, 322 (3.1%) subjects had ICAS. Subjects with ICAS were older, and had higher mean values for fasting glucose, body mass index and blood pressure compared with those without ICAS. Subjects with ICAS had significantly lower muscle mass, SMI and higher percent body fat compared with those without ICAS. In logistic regression analysis, the subjects in the highest tertile of muscle mass had the lowest odds ratio for ICAS with the lowest tertile group of muscle mass as the reference group even after adjusting for age, systolic blood pressure, fasting blood glucose, sex, smoking and exercise (OR 0.650, 95% CI 0.442-0.955). Subjects with ICAS had significantly decreased muscle mass compared with those without ICAS in Korean adults. The risk for ICAS was lower in subjects with higher muscle mass. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Phosphodiesterases regulate airway smooth muscle function in health and disease.

    Science.gov (United States)

    Krymskaya, Vera P; Panettieri, Reynold A

    2007-01-01

    On the basis of structure, regulation, and kinetic properties, phosphodiesterases (PDEs) represent a superfamily of enzymes divided into 11 subfamilies that catalyze cytosolic levels of 3',5'-cyclic adenosine monophosphate (cAMP) or 3',5'-cyclic guanosine monophosphate (cGMP) to 5'-AMP or 5'-GMP, respectively. PDE4 represents the major PDE expressed in inflammatory cells as well as airway smooth muscle (ASM), and selective PDE4 inhibitors provide a broad spectrum of anti-inflammatory effects such as abrogating cytokine and chemokine release from inflammatory cells and inhibiting inflammatory cell trafficking. Due to cell- and tissue-specific gene expression and regulation, PDEs modulate unique organ-based functions. New tools or compounds that selectively inhibit PDE subfamilies and genetically engineered mice deficient in selective isoforms have greatly enhanced our understanding of PDE function in airway inflammation and resident cell function. This chapter will focus on recent advances in our understanding of the role of PDE in regulating ASM function.

  6. Fasting- and Exercise-Induced PDH Regulation in Skeletal Muscle

    DEFF Research Database (Denmark)

    Gudiksen, Anders

    in selected mitochondrial proteins. Lastly, increased oxidative capacity leads to exercise-induced skeletal muscle PDH activation that is closely matched to the relative exercise intensity at submaximal exercise, while reaching a higher level at maximal exercise in trained individuals. These responses......Pyruvate dehydrogenase PDH constitutes the only mammalian pathway for irreversible conversion of pyruvate to acetyl-CoA thus providing the vital link between glycolytic energy production, the TCA cycle, and oxidative phosphorylation. Because the PDC controls the conversion of pyruvate it occupies...... a central position in relation to the control of mitochondrial energy production and cellular substrate metabolism. Suppression and activation of PDH becomes essential in situations where glucose availability and/or use changes with swift and appropriate regulation of the complex to maintain energy...

  7. Abelson tyrosine-protein kinase 2 regulates myoblast proliferation and controls muscle fiber length.

    Science.gov (United States)

    Lee, Jennifer K; Hallock, Peter T; Burden, Steven J

    2017-12-12

    Muscle fiber length is nearly uniform within a muscle but widely different among different muscles. We show that Abelson tyrosine-protein kinase 2 (Abl2) has a key role in regulating myofiber length, as a loss of Abl2 leads to excessively long myofibers in the diaphragm, intercostal and levator auris muscles but not limb muscles. Increased myofiber length is caused by enhanced myoblast proliferation, expanding the pool of myoblasts and leading to increased myoblast fusion. Abl2 acts in myoblasts, but as a consequence of expansion of the diaphragm muscle, the diaphragm central tendon is reduced in size, likely contributing to reduced stamina of Abl2 mutant mice. Ectopic muscle islands, each composed of myofibers of uniform length and orientation, form within the central tendon of Abl2 +/- mice. Specialized tendon cells, resembling tendon cells at myotendinous junctions, form at the ends of these muscle islands, suggesting that myofibers induce differentiation of tendon cells, which reciprocally regulate myofiber length and orientation.

  8. SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation

    DEFF Research Database (Denmark)

    Petersson, Stine Juhl; Jørgensen, Louise Helskov; Andersen, Ditte C.

    2013-01-01

    Skeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up......-regulated during skeletal muscle disease, but its function remains elusive. In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6......, Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen...

  9. Sarcopenia and Predictors of Skeletal Muscle Mass in Elderly Men With and Without Obesity

    Directory of Open Access Journals (Sweden)

    Katja Stoever MA

    2017-06-01

    Full Text Available Objectives: The aim of this study was to determine the variables which show the highest association with muscle mass and to identify the most important predictors for muscle mass in elderly men with and without sarcopenia. Methods: A total of 71 men participated, aged ≥65 years. Sarcopenia was assessed using the definition of the European Working Group on Sarcopenia in Older People with determining skeletal muscle index (SMI, hand-grip strength (HGS, and Short Physical Performance Battery. In addition, maximum strength at upper and lower extremities and physical activity were measured. Results: Strong correlations existed between SMI and gait speed, HGS, maximum isometric strength at leg and chest press. Physical activity showed low correlations with muscle strength. Regression analysis revealed HGS and gait speed as key predictors for SMI. Discussion: The recommendation is measuring gait speed and HGS in clinical practice at first followed by measuring muscle mass for determining sarcopenia.

  10. Abelson tyrosine-protein kinase 2 Regulates Myoblast Proliferation and Controls Muscle Fiber Length

    OpenAIRE

    Burden, Steven; Lee, Jennifer

    2017-01-01

    Muscle fiber length is nearly uniform within a muscle but widely different among muscles. Here, we show that Abelson tyrosine-protein kinase 2 (Abl2) has a key role in regulating myofiber length, as a loss of Abl2 leads to excessively long myofibers in the diaphragm and other muscles. Increased myofiber length is caused by enhanced myoblast proliferation, expanding the pool of available myoblasts and leading to increased myoblast fusion. Abl2 acts in myoblasts, but expansion of the diaphragm ...

  11. Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

    Directory of Open Access Journals (Sweden)

    Sara H Windahl

    Full Text Available Androgens are important regulators of bone mass but the relative importance of testosterone (T versus dihydrotestosterone (DHT for the activation of the androgen receptor (AR in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2, encoded by separate genes (Srd5a1 and Srd5a2. 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05 and cortical bone mineral content (-15%, p<0.05 but unchanged serum androgen levels compared with wild type (WT mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05 in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05. Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

  12. Deficits in muscle strength, mass, quality and mobility in people with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Roig, Marc; Eng, Janice J; MacIntyre, Donna L

    2011-01-01

    PURPOSE: Midthigh intramuscular fat (IF), a feature of reduced muscle quality, is an important predictor of self-reported mobility loss in the elderly. This study compared measures of muscle strength, mass, IF, and mobility in patients with chronic obstructive pulmonary disease (COPD) and healthy...

  13. Levator claviculae muscle presenting as a hard clavicular mass: imaging study

    International Nuclear Information System (INIS)

    Ruiz Santiago, F.; Lopez Milena, G.; Tristan Fernandez, J.M.; Chamorro Santos, C.

    2001-01-01

    We report a case of levator claviculae muscle presenting clinically as a hard mass in the clavicular area due to angular deformity of this bone. To our knowledge, this is the first report where the anomalous muscle shows this clinical presentation. (orig.)

  14. The Impact of Low Muscle Mass Definition on the Prevalence of Sarcopenia in Older Australians

    Directory of Open Access Journals (Sweden)

    Solomon Yu

    2014-01-01

    Full Text Available Background. Sarcopenia is the presence of low muscle mass and low muscle function. The aim of this study was to establish cutoffs for low muscle mass using three published methods and to compare the prevalence of sarcopenia in older Australians. Methods. Gender specific cutoffs levels were identified for low muscle mass using three different methods. Low grip strength was determined using established cutoffs of <30 kg for men and <20 kg for women to estimate the prevalence of sarcopenia. Results. Gender specific cutoffs levels for low muscle mass identified were (a <6.89 kg/m2 for men and <4.32 kg/m2 for women, <2 standard deviation (SD of a young reference population; (b <7.36 kg/m2 for men and <5.81 kg/m2 for women from the lowest 20% percentile of the older group; and (c <−2.15 for men and <−1.42 for women from the lowest 20% of the residuals of linear regressions of appendicular skeletal mass, adjusted for fat mass and height. Prevalence of sarcopenia in older (65 years and older people by these three methods for men was 2.5%, 6.2%, and 6.4% and for women 0.3%, 9.3%, and 8.5%, respectively. Conclusions. Sarcopenia is common but consensus on the best method to confirm low muscle mass is required.

  15. Positive muscle protein net balance and differential regulation of atrogene expression after resistance exercise and milk protein supplementation

    DEFF Research Database (Denmark)

    Reitelseder, Søren; Agergaard, Jakob; Doessing, Simon

    2014-01-01

    Purpose Resistance exercise and amino acid availability are positive regulators of muscle protein net balance (NB). However, anabolic responses to resistance exercise and protein supplementation deserve further elucidation. The purpose was to compare intakes of whey, caseinate (both: 0.30 g/kg lean...... body mass), or a non-caloric control after heavy resistance exercise on protein turnover and mRNA expressions of forkhead homeobox type O (FOXO) isoforms, muscle RING finger 1 (MuRF1), and Atrogin1 in young healthy males. Methods Protein turnover was determined by stable isotope-labeled leucine...

  16. Prevalence of skeletal muscle mass loss and its association with swallowing function after cardiovascular surgery.

    Science.gov (United States)

    Wakabayashi, Hidetaka; Takahashi, Rimiko; Watanabe, Naoko; Oritsu, Hideyuki; Shimizu, Yoshitaka

    2017-06-01

    The aim of this study was to assess the prevalence of skeletal muscle mass loss and its association with swallowing function in patients with dysphagia after cardiovascular surgery. A retrospective cohort study was performed in 65 consecutive patients with dysphagia after cardiovascular surgery who were prescribed speech therapy. Skeletal muscle index (SMI) was calculated as total psoas muscle area assessed via abdominal computed tomography divided by height squared. Cutoff values were 6.36 cm 2 /m 2 for men and 3.92 cm 2 /m 2 for women. The Food Intake Level Scale (FILS) was used to assess the swallowing function. Univariate and ordered logistic regression analyses were applied to examine the associations between skeletal muscle mass loss and dysphagia. The study included 50 men and 15 women (mean age 73 ± 8 y). The mean SMI was 4.72 ± 1.37 cm 2 /m 2 in men and 3.33 ± 1.42 cm 2 /m 2 in women. Skeletal muscle mass loss was found in 53 (82%) patients. Twelve had tracheostomy cannula. Thirteen were non-oral feeding (FILS levels 1-3), 5 were oral food intake and alternative nutrition (levels 4-6), and 47 were oral food intake alone (levels 7-9) at discharge. The FILS at discharge was significantly lower in patients with skeletal muscle mass loss. Ordered logistic regression analysis of swallowing function showed that skeletal muscle mass loss and tracheostomy cannula were associated independently with the FILS at discharge. The prevalence of skeletal muscle mass loss is very high, and skeletal muscle mass loss is associated with swallowing function. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Regulation of gene expression in vertebrate skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Carvajal, Jaime J., E-mail: jaime.carvajal@icr.ac.uk; Rigby, Peter W.J., E-mail: peter.rigby@icr.ac.uk

    2010-11-01

    During embryonic development the integration of numerous synergistic signalling pathways turns a single cell into a multicellular organism with specialized cell types and highly structured, organized tissues. To achieve this, cells must grow, proliferate, differentiate and die according to their spatiotemporal position. Unravelling the mechanisms by which a cell adopts the correct fate in response to its local environment remains one of the fundamental goals of biological research. In vertebrates skeletal myogenesis is coordinated by the activation of the myogenic regulatory factors (MRFs) in response to signals that are interpreted by their associated regulatory elements in different precursor cells during development. The MRFs trigger a cascade of transcription factors and downstream structural genes, ultimately resulting in the generation of one of the fundamental histotypes. In this review we discuss the regulation of the different MRFs in relation to their position in the myogenic cascade, the changes in the general transcriptional machinery during muscle differentiation and the emerging importance of miRNA regulation in skeletal myogenesis.

  18. Adiposity, muscle mass and muscle strength in relation to functional decline in older persons.

    NARCIS (Netherlands)

    Schaap, L.A.; Koster, A.; Visser, M.

    2013-01-01

    Aging is associated with changes in body composition and muscle strength. This review aimed to determine the relation between different body composition measures and muscle strength measures and functional decline in older men and women. By use of relevant databases (PubMed, Embase, and CINAHL) and

  19. Effects of IL-6 on pyruvate dehydrogenase regulation in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup; Knudsen, Jakob Grunnet; Brandt, Nina

    2014-01-01

    Skeletal muscle regulates substrate choice according to demand and availability and pyruvate dehydrogenase (PDH) is central in this regulation. Circulating interleukin (IL)-6 increases during exercise and IL-6 has been suggested to increase whole body fat oxidation. Furthermore, IL-6 has been...... reported to increase AMP-activated protein kinase (AMPK) phosphorylation and AMPK suggested to regulate PDHa activity. Together, this suggests that IL-6 may be involved in regulating PDH. The aim of this study was to investigate the effect of a single injection of IL-6 on PDH regulation in skeletal muscle...... in fed and fasted mice. Fed and 16-18 h fasted mice were injected with either 3 ng · g(-1) recombinant mouse IL-6 or PBS as control. Fasting markedly reduced plasma glucose, muscle glycogen, muscle PDHa activity, as well as increased PDK4 mRNA and protein content in skeletal muscle. IL-6 injection did...

  20. Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin

    Science.gov (United States)

    Winbanks, Catherine E.; Weeks, Kate L.; Thomson, Rachel E.; Sepulveda, Patricio V.; Beyer, Claudia; Qian, Hongwei; Chen, Justin L.; Allen, James M.; Lancaster, Graeme I.; Febbraio, Mark A.; Harrison, Craig A.; McMullen, Julie R.; Chamberlain, Jeffrey S.

    2012-01-01

    Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed follistatin-induced Akt/mTOR/S6K signaling. Importantly, the regulation of Smad3- and mTOR-dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin. These findings identify a critical role of Smad3/Akt/mTOR/S6K/S6RP signaling in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms. PMID:22711699

  1. The influence of different muscle mass measurements on the diagnosis of cancer cachexia.

    Science.gov (United States)

    Blauwhoff-Buskermolen, Susanne; Langius, Jacqueline A E; Becker, Annemarie; Verheul, Henk M W; de van der Schueren, Marian A E

    2017-08-01

    Progressive loss of muscle mass is a major characteristic of cancer cachexia. Consensus definitions for cachexia provide different options to measure muscle mass. This study describes the effect of different methods to determine muscle mass on the diagnosis of cancer cachexia. In addition, the association of cachexia with other features of cachexia, quality of life, and survival was explored. Prior to chemotherapy, cachexia was assessed by weight loss, body mass index, and muscle mass measurements, the latter by mid-upper arm muscle area (MUAMA), computed tomography (CT) scans, and bio-electrical impedance analysis (BIA). In addition, appetite, inflammation, muscle strength, fatigue, quality of life, and survival were measured, and associations with cachexia were explored. Included were 241 patients with advanced cancer of the lung (36%), colon/rectum (31%), prostate (18%), or breast (15%). Mean age was 64 ± 10 years; 54% was male. Prevalence of low muscle mass was as follows: 13% with MUAMA, 59% with CT, and 93% with BIA. In turn, the prevalence of cachexia was 37, 43, and 48%, whereby weight loss >5% was the most prominent component of being defined cachectic. Irrespective of type of muscle measurement, patients with cachexia presented more often with anorexia, inflammation, low muscle strength, and fatigue and had lower quality of life. Patients with cachexia had worse overall survival compared with patients without cachexia: HRs 2.00 (1.42-2.83) with MUAMA, 1.64 (1.15-2.34) with CT, and 1.50 (1.05-2.14) with BIA. Although the prevalence of low muscle mass in patients with cancer depended largely on the type of muscle measurement, this had little influence on the diagnosis of cancer cachexia (as the majority of patients was already defined cachectic based on weight loss). New studies are warranted to further elucidate the additional role of muscle measurements in the diagnosis of cachexia and the association with clinical outcomes. © 2017 The Authors

  2. Ca2+-Dependent Regulations and Signaling in Skeletal Muscle: From Electro-Mechanical Coupling to Adaptation

    Science.gov (United States)

    Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

    2015-01-01

    Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca2+ ions in adult muscle but also highlight recent findings of critical Ca2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance. PMID:25569087

  3. Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells.

    Science.gov (United States)

    Tosic, Milica; Allen, Anita; Willmann, Dominica; Lepper, Christoph; Kim, Johnny; Duteil, Delphine; Schüle, Roland

    2018-01-25

    Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.

  4. Electrical stimulation as a biomimicry tool for regulating muscle cell behavior.

    Science.gov (United States)

    Ahadian, Samad; Ostrovidov, Serge; Hosseini, Vahid; Kaji, Hirokazu; Ramalingam, Murugan; Bae, Hojae; Khademhosseini, Ali

    2013-01-01

    There is a growing need to understand muscle cell behaviors and to engineer muscle tissues to replace defective tissues in the body. Despite a long history of the clinical use of electric fields for muscle tissues in vivo, electrical stimulation (ES) has recently gained significant attention as a powerful tool for regulating muscle cell behaviors in vitro. ES aims to mimic the electrical environment of electroactive muscle cells (e.g., cardiac or skeletal muscle cells) by helping to regulate cell-cell and cell-extracellular matrix (ECM) interactions. As a result, it can be used to enhance the alignment and differentiation of skeletal or cardiac muscle cells and to aid in engineering of functional muscle tissues. Additionally, ES can be used to control and monitor force generation and electrophysiological activity of muscle tissues for bio-actuation and drug-screening applications in a simple, high-throughput, and reproducible manner. In this review paper, we briefly describe the importance of ES in regulating muscle cell behaviors in vitro, as well as the major challenges and prospective potential associated with ES in the context of muscle tissue engineering.

  5. Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle.

    Science.gov (United States)

    Sylow, Lykke; Jensen, Thomas E; Kleinert, Maximilian; Mouatt, Joshua R; Maarbjerg, Stine J; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A

    2013-04-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (~60-100%) and humans (~40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20-58% in extensor digitorum longus (EDL; P contraction-stimulated increment in glucose uptake was decreased by 27% (P = 0.1) and 40% (P muscles, respectively, of muscle-specific inducible Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P muscles, respectively. These are the first data to show that Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake.

  6. Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans

    Science.gov (United States)

    Walker, Ann C.; O'Connor-Semmes, Robin L.; Leonard, Michael S.; Miller, Ram R.; Stimpson, Stephen A.; Turner, Scott M.; Ravussin, Eric; Cefalu, William T.; Hellerstein, Marc K.; Evans, William J.

    2014-01-01

    Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19–30 yr, 70–84 yr), 15 postmenopausal women (51–62 yr, 70–84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA. PMID:24764133

  7. Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Kristen A Baltgalvis

    Full Text Available BACKGROUND: Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17beta-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. METHODOLOGY/PRINCIPAL FINDINGS: Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17beta-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERalpha was the most abundant, followed by Gper and ERbeta in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERalpha gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17beta-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. CONCLUSIONS/SIGNIFICANCE: These data suggest that Gpx3 and ERalpha gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERalpha on Gpx3 expression in skeletal muscle, and their importance in the

  8. EBF proteins participate in transcriptional regulation of Xenopus muscle development.

    Science.gov (United States)

    Green, Yangsook Song; Vetter, Monica L

    2011-10-01

    EBF proteins have diverse functions in the development of multiple lineages, including neurons, B cells and adipocytes. During Drosophila muscle development EBF proteins are expressed in muscle progenitors and are required for muscle cell differentiation, but there is no known function of EBF proteins in vertebrate muscle development. In this study, we examine the expression of ebf genes in Xenopus muscle tissue and show that EBF activity is necessary for aspects of Xenopus skeletal muscle development, including somite organization, migration of hypaxial muscle anlagen toward the ventral abdomen, and development of jaw muscle. From a microarray screen, we have identified multiple candidate targets of EBF activity with known roles in muscle development. The candidate targets we have verified are MYOD, MYF5, M-Cadherin and SEB-4. In vivo overexpression of the ebf2 and ebf3 genes leads to ectopic expression of these candidate targets, and knockdown of EBF activity causes downregulation of the endogenous expression of the candidate targets. Furthermore, we found that MYOD and MYF5 are likely to be direct targets. Finally we show that MYOD can upregulate the expression of ebf genes, indicating the presence of a positive feedback loop between EBF and MYOD that we find to be important for maintenance of MYOD expression in Xenopus. These results suggest that EBF activity is important for both stabilizing commitment and driving aspects of differentiation in Xenopus muscle cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure.

    Science.gov (United States)

    Lang, C C; Chomsky, D B; Rayos, G; Yeoh, T K; Wilson, J R

    1997-01-01

    The purpose of this study was to determine whether skeletal muscle atrophy limits the maximal exercise capacity of stable ambulatory patients with heart failure. Body composition and maximal exercise capacity were measured in 100 stable ambulatory patients with heart failure. Body composition was assessed by using dual-energy X-ray absorption. Peak exercise oxygen consumption (VO2peak) and the anaerobic threshold were measured by using a Naughton treadmill protocol and a Medical Graphics CardioO2 System. VO2peak averaged 13.4 +/- 3.3 ml.min-1.kg-1 or 43 +/- 12% of normal. Lean body mass averaged 52.9 +/- 10.5 kg and leg lean mass 16.5 +/- 3.6 kg. Leg lean mass correlated linearly with VO2peak (r = 0.68, P < 0.01), suggesting that exercise performance is influences by skeletal muscle mass. However, lean body mass was comparable to levels noted in 1,584 normal control subjects, suggesting no decrease in muscle mass. Leg muscle mass was comparable to levels noted in 34 normal control subjects, further supporting this conclusion. These findings suggest that exercise intolerance in stable ambulatory patients with heart failure is not due to skeletal muscle atrophy.

  10. The Effects of Muscle Mass on Homocyst(e)ine Levels in Plasma and Urine.

    Science.gov (United States)

    Malinow, M René; Lister, Craig L; DE Crée, Carl

    The present study was designed to examine the relationship between homocyst(e)ine (H[e]) levels and muscle mass. Two experimental groups each of 24 Caucasian males, one consisting of higher-muscle mass subjects (HMM) and the other of lower-muscle mass subjects (LMM) participated in this study. Muscle mass was estimated from 24-hour urine collections of creatinine (Crt). Muscle mass was 40.3 ± 15.9 kg in HMM and 37.2 ± 11.4 kg in LMM (P= 0.002). Mean plasma H(e) levels in HMM were 10.29 ± 2.9 nmol/mL, and in LMM were 10.02 ± 2.4 nmol/L (Not significant, [NS]). Urinary H(e) levels (UH[e]) were 9.95 ± 4.3 nmol/mL and 9.22 ± 2.9 nmol/mL for HMM and LMM, respectively (NS). Plasma H(e) levels correlated well with UH(e) (HMM: r= 0.58, P= 0.009; LMM: r= 0.66, P= 0.004). Muscle mass and was not correlated to either plasma H(e) or UH(e). However, in HMM trends were identified for body mass to be correlated with UH(e) (r= 0.39, P= 0.10) and UCrt (r= 0.41, P= 0.08). Surprisingly, in HMM plasma and UCrt were only weakly correlated (r= 0.44, P= 0.06). Our results do not support a causal relationship between the amount of muscle mass and H(e) levels in plasma or urine.

  11. Dynamic Regulation of Sarcomeric Actin Filaments in Striated Muscle

    OpenAIRE

    Ono, Shoichiro

    2010-01-01

    In striated muscle, the actin cytoskeleton is differentiated into myofibrils. Actin and myosin filaments are organized in sarcomeres and specialized for producing contractile forces. Regular arrangement of actin filaments with uniform length and polarity is critical for the contractile function. However, the mechanisms of assembly and maintenance of sarcomeric actin filaments in striated muscle are not completely understood. Live imaging of actin in striated muscle has revealed that actin sub...

  12. The impact of low muscle mass definition on the prevalence of sarcopenia in older Australians.

    Science.gov (United States)

    Yu, Solomon; Appleton, Sarah; Adams, Robert; Chapman, Ian; Wittert, Gary; Visvanathan, Thavarajah; Visvanathan, Renuka

    2014-01-01

    Sarcopenia is the presence of low muscle mass and low muscle function. The aim of this study was to establish cutoffs for low muscle mass using three published methods and to compare the prevalence of sarcopenia in older Australians. Gender specific cutoffs levels were identified for low muscle mass using three different methods. Low grip strength was determined using established cutoffs of standard deviation (SD) of a young reference population; (b) <7.36 kg/m(2) for men and <5.81 kg/m(2) for women from the lowest 20% percentile of the older group; and (c) <-2.15 for men and <-1.42 for women from the lowest 20% of the residuals of linear regressions of appendicular skeletal mass, adjusted for fat mass and height. Prevalence of sarcopenia in older (65 years and older) people by these three methods for men was 2.5%, 6.2%, and 6.4% and for women 0.3%, 9.3%, and 8.5%, respectively. Sarcopenia is common but consensus on the best method to confirm low muscle mass is required.

  13. Locomotion and muscle mass measures in a murine model of collagen-induced arthritis

    NARCIS (Netherlands)

    Hartog, A.; Hulsman, J.; Garssen, J.

    2009-01-01

    Background: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and

  14. Peak muscle mass in young men and sarcopenia in the ageing male

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost Munk; Nielsen, T L; Brixen, K

    2015-01-01

    of sarcopenia in men. INTRODUCTION: The ageing population increases the prevalence of sarcopenia. Estimation of normative data on muscle mass in young men during the peak of anabolic hormones is necessary for the diagnosis of sarcopenia in ageing males. The purposes of this study were to provide population......The prevalence of sarcopenia increases with age. The diagnosis of sarcopenia relies in part on normative data on muscle mass, but these data are lacking. This study provides population-based reference data on muscle mass in young men, and these results may be used clinically for the diagnosis......-based reference data on lean body mass (LBM) in young men during the time of peak levels of GH/IGF-1 and testosterone and further to apply the reference data on a population-based sample of men aged 60-74 years to estimate the prevalence of sarcopenia. METHODS: This is a cross-sectional, population-based single...

  15. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats.

    Science.gov (United States)

    Grubbe, M-C; Thomsen, J S; Nyengaard, J R; Duruox, M; Brüel, A

    2014-12-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (aBMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, Pbone strength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P<0.001), and tended to prevent loss of muscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse-induced loss of periosteal BFR/BS at the mid-femur and rectus femoris muscle mass.

  16. Rac1- a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian

    2014-01-01

    -stimulated glucose uptake in skeletal muscle, since muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake in skeletal muscle. The molecular mechanisms by which Rac1 regulate glucose uptake is presently unknown. However, recent studies link Rac1......Muscle contraction stimulates muscle glucose uptake by facilitating translocation of the glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibers. However, the intracellular mechanisms regulating this process are not well...... understood. The GTPase, Rac1 has, until recently, only been investigated with regards to its involvement in insulin-stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise/contraction...

  17. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Nesterov, Sergey V; Kemppainen, Jukka

    2007-01-01

    receptor blockade. BF heterogeneity within muscles was calculated from 16-mm(3) voxels in BF images and heterogeneity among the muscles from the mean values of the four QF compartments. Mean BF in the whole QF and its four parts increased, and heterogeneity decreased with workload both without......Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF...... and with theophylline (P heterogeneity among the QF muscles, yet blockade increased within-muscle BF heterogeneity in all four QF muscles (P = 0.03). Taken together, these results show that BF becomes less heterogeneous with increasing...

  18. Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1.

    Science.gov (United States)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

    2015-02-01

    Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30-50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40-50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30-40% in tension developing muscle but did not affect contraction-stimulated glucose transport in

  19. Ultrasonography to Measure Swallowing Muscle Mass and Quality in Older Patients With Sarcopenic Dysphagia.

    Science.gov (United States)

    Ogawa, Nami; Mori, Takashi; Fujishima, Ichiro; Wakabayashi, Hidetaka; Itoda, Masataka; Kunieda, Kenjiro; Shigematsu, Takashi; Nishioka, Shinta; Tohara, Haruka; Yamada, Minoru; Ogawa, Sumito

    2018-06-01

    Sarcopenic dysphagia is characterized by difficulty swallowing due to a loss of whole-body skeletal and swallowing muscle mass and function. However, no study has reported on swallowing muscle mass and quality in patients with sarcopenic dysphagia. To compare the differences in swallowing muscle mass and quality between sarcopenic and nonsarcopenic dysphagia. A cross-sectional study was performed in 55 older patients, who had been recommended to undergo dysphagia assessment and/or rehabilitation. Sarcopenic dysphagia was diagnosed using a diagnostic algorithm for sarcopenic dysphagia. The thickness and area of tongue muscle and geniohyoid muscle (coronal plane and sagittal plane), and the echo-intensity of the tongue and geniohyoid muscles were examined by ultrasound. The study participants included 31 males and 24 females (mean age of 82 ± 7 years), with 14 having possible sarcopenic dysphagia, 22 probable sarcopenic dysphagia, and 19 without sarcopenic dysphagia. The group with sarcopenic dysphagia had a significantly lower cross-sectional area and area of brightness of the tongue muscle than that observed in the group without sarcopenic dysphagia. The most specific factor for identifying the presence of sarcopenic dysphagia was tongue muscle area (sensitivity, 0.389; specificity, 0.947; cut-off value, 1536.0), while the factor with the highest sensitivity was geniohyoid muscle area brightness in sagittal sections (sensitivity, 0.806; specificity, 0.632; cut-off value, 20.1). Multivariate logistic regression analysis showed that the area of the tongue muscle and its area of brightness were independent risk factors for sarcopenic dysphagia. However, geniohyoid sagittal muscle area and area of brightness showed no significant independent association with sarcopenic dysphagia. Tongue muscle mass in patients with sarcopenic dysphagia was smaller than that in patients without the condition. Sarcopenic dysphagia was also associated with increased intensity of the

  20. Tinetti mobility test is related to muscle mass and strength in non-institutionalized elderly people.

    Science.gov (United States)

    Curcio, Francesco; Basile, Claudia; Liguori, Ilaria; Della-Morte, David; Gargiulo, Gaetano; Galizia, Gianluigi; Testa, Gianluca; Langellotto, Assunta; Cacciatore, Francesco; Bonaduce, Domenico; Abete, Pasquale

    2016-12-01

    Elderly people are characterized by a high prevalence of falls and sarcopenia. However, the relationship among Tinetti mobility test (TMT) score, a powerful tool to detect elderly people at risk of falls, and sarcopenia is still not thoroughly investigated. Thus, to determine the relationship between TMT score and muscle mass and strength, 337 elderly participants (mean age 77.1 ± 6.9 years) admitted to comprehensive geriatric assessment were enrolled. TMT score, muscle mass by bioimpedentiometer, and muscle strength by grip strength were evaluated. Muscle mass progressively decreased as TMT score decreased (from 15.3 ± 3.7 to 8.8 ± 1.8 kg/m 2 ; p for trend strength decreased progressively as Tinetti score decreased (from 34.7 ± 8.0 to 23.7 ± 8.7 kg; p for trend 0.001). Linear regression analysis demonstrated that TMT score is linearly related with muscle mass (y = 4.5x + 0.4, r = 0.61; p strength (y = 14.0x + 0.8, r = 0.53; p strength (r = 0.39, p = 0.046). The present study indicates that TMT score is significantly related to muscle mass and strength in non-institutionalized elderly participants. This evidence suggests that TMT score, together with evaluation of muscle mass and strength, may identify sarcopenic elderly participants at high risk of falls.

  1. Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

    Science.gov (United States)

    Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

    1987-01-01

    The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

  2. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

    Science.gov (United States)

    Chaillou, Thomas; Lanner, Johanna T

    2016-12-01

    Reduced oxygen (O 2 ) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O 2 level could affect their activity during muscle regeneration. In this review, we present the idea that O 2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O 2 levels to promote muscle regeneration. Severe hypoxia (≤1% O 2 ) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O 2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity. © FASEB.

  3. Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Madsen, Agnete Louise Bjerregaard; Kleinert, Maximilian

    2016-01-01

    Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one-legged exer......Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one......-legged exercise training as well as in response to subsequent insulin stimulation in exercised and non-exercised human muscle. Acute one-legged exercise decreased (phuman muscle....... The decrease in LC3-II/LC3-I ratio did not correlate with activation of AMPK trimer complexes in human muscle. Consistently, pharmacological AMPK activation with AICAR in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (p

  4. Regulation of GPCR-mediated smooth muscle contraction : implications for asthma and pulmonary hypertension

    NARCIS (Netherlands)

    Wright, D B; Tripathi, S; Sikarwar, A; Santosh, K T; Perez-Zoghbi, J; Ojo, O O; Irechukwu, N; Ward, J P T; Schaafsma, D

    Contractile G-protein-coupled receptors (GPCRs) have emerged as key regulators of smooth muscle contraction, both under healthy and diseased conditions. This brief review will discuss some key topics and novel insights regarding GPCR-mediated airway and vascular smooth muscle contraction as

  5. Regulation of slow and fast muscle myofibrillogenesis by Wnt/beta-catenin and myostatin signaling.

    NARCIS (Netherlands)

    Tee, J.M.; van Rooijen, C.R.; Boonen, R.A.C.M.; Zivkovic, D.

    2009-01-01

    Deviation from proper muscle development or homeostasis results in various myopathic conditions. Employing genetic as well as chemical intervention, we provide evidence that a tight regulation of Wnt/beta-catenin signaling is essential for muscle fiber growth and maintenance. In zebrafish embryos,

  6. Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Parker, Benjamin L; Fritzen, Andreas Mæchel

    2017-01-01

    Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induc...

  7. Low muscle mass--tall and obese children a special genre of obesity.

    Science.gov (United States)

    Ralt, Dina

    2007-01-01

    The prevalence of over-weight and obesity has increased markedly in the last two decades and vast international resources have been directed toward researching these issues. Obesity would appear to be a problem that is easy to resolve: just eat less and move more. However, this very common condition has turned out to be extremely troublesome, and in some cases even insolvable. A perspective is presented here suggesting that some of the insoluble cases of obesity are the result of an inborn condition of a very low muscle mass. The interplay between less muscle and more fat tissue is discussed from physiological and environmental perspectives with an emphasis on the early years of childhood. It is proposed that these interactions lead to bodily economic decisions sliding between thrift or prodigal strategies. The thrift strategy results not only in obesity and less physical activity but also in other maladies which the body is unable to manage. What leads to obesity (less muscle, more fat) in the medial population will result in morbid obesity when the children are short of muscle tissue from the start. Attempts to lessen the consequences of low muscle mass, which might be very difficult at adulthood, can be more fruitful if initiated at childhood. Early recognition of the ailment is thus crucial. Based on studies demonstrating a 'rivalry' between muscle build-up and height growth at childhood, it is postulated that among the both taller and more obese children the percentage of children with lower muscle mass will be significant. A survey of the height and BMI (Body Mass Index) of Israeli fifth graders supports this postulation. A special, body/muscle-building gymnastics program for children is suggested as a potential early intervention to partially prevent this type of almost irreversible ill progress of obesity.

  8. Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice

    OpenAIRE

    Lang, Susan M.; Kazi, Abid A.; Hong-Brown, Ly; Lang, Charles H.

    2012-01-01

    The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/-) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated ...

  9. Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

    Science.gov (United States)

    Fritzen, Andreas M.; Madsen, Agnete B.; Kleinert, Maximilian; Treebak, Jonas T.; Lundsgaard, Anne‐Marie; Jensen, Thomas E.; Richter, Erik A.; Wojtaszewski, Jørgen; Kiens, Bente

    2016-01-01

    Key points Regulation of autophagy in human muscle in many aspects differs from the majority of previous reports based on studies in cell systems and rodent muscle.An acute bout of exercise and insulin stimulation reduce human muscle autophagosome content.An acute bout of exercise regulates autophagy by a local contraction‐induced mechanism.Exercise training increases the capacity for formation of autophagosomes in human muscle.AMPK activation during exercise seems insufficient to regulate autophagosome content in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy‐inhibiting effect of insulin. Abstract Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one‐legged exercise, one‐legged exercise training and subsequent insulin stimulation in exercised and non‐exercised human muscle. Acute one‐legged exercise decreased (Pexercise in human muscle. The decrease in LC3‐II/LC3‐I ratio did not correlate with activation of 5′AMP activated protein kinase (AMPK) trimer complexes in human muscle. Consistently, pharmacological AMPK activation with 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) in mouse muscle did not affect the LC3‐II/LC3‐I ratio. Four hours after exercise, insulin further reduced (Pexercised and non‐exercised leg in humans. This coincided with increased Ser‐757 phosphorylation of Unc51 like kinase 1 (ULK1), which is suggested as a mammalian target of rapamycin complex 1 (mTORC1) target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3‐II/LC3‐I ratio. In response to 3 weeks of one‐legged exercise training, the LC3‐II/LC3‐I ratio decreased (Pexercise and insulin stimulation reduce muscle autophagosome content, while exercise

  10. mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3

    Directory of Open Access Journals (Sweden)

    Maximilian Kleinert

    2016-08-01

    Conclusions: We identified a novel link between mTORC2 and PLIN3, which regulates lipid storage in muscle. While mTORC2 is a negative regulator, we further identified AMPK as a positive regulator of PLIN3, which impacts whole-body substrate utilization and nutrient partitioning.

  11. Impaired physical function, loss of muscle mass and assessment of biomechanical properties in critical ill patients

    DEFF Research Database (Denmark)

    Poulsen, Jesper Brøndum

    2012-01-01

    Intensive care unit (ICU) admission is associated with muscle weakness and ICU survivors report sustained limitation of physical capacity for years after discharge. Limited information is available on the underlying biomechanical properties responsible for this muscle function impairment. A plaus......Intensive care unit (ICU) admission is associated with muscle weakness and ICU survivors report sustained limitation of physical capacity for years after discharge. Limited information is available on the underlying biomechanical properties responsible for this muscle function impairment....... A plausible contributor to the accentuated catabolic drive in ICU patients is a synergistic response to inflammation and inactivity leading to loss of muscle mass. As these entities are predominantly present in the early phase of ICU stay, interventions employed during this time frame may exhibit the greatest...... potential to counteract loss of muscle mass. Despite the obvious clinical significance of muscle atrophy for the functional impairment observed in ICU survivors, no preventive therapies have been identified as yet. The overall aim of the present dissertation is to characterize aspects of physical function...

  12. The loss of skeletal muscle strength, mass, and quality in older adults : the health, aging and body composition study

    NARCIS (Netherlands)

    Goodpaster, Bret H; Park, Seok Won; Harris, Tamara B; Kritchevsky, Steven B; Nevitt, Michael; Schwartz, Ann V; Simonsick, Eleanor M; Tylavsky, Frances A; Visser, Marjolein; Newman, Anne B

    2006-01-01

    BACKGROUND: The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. METHODS: Three-year changes in muscle mass and strength were

  13. Creatinine excretion rate, a marker of muscle mass, is related to clinical outcome in patients with chronic systolic heart failure

    NARCIS (Netherlands)

    ter Maaten, Jozine M.; Damman, Kevin; Hillege, Hans L.; Bakker, Stephan J.; Anker, Stefan D.; Navis, Gerjan; Voors, Adriaan A.

    2014-01-01

    Aims In chronic heart failure (CHF), low body mass as a reflection of low muscle mass has been associated with poor outcome. Urinary creatinine excretion rate (CER) is an established marker of muscle mass, but has not been investigated in CHF. This study aims to evaluate urinary CER as a marker of

  14. An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: potential role in the treatment of sarcopenic obesity.

    Science.gov (United States)

    Kirk-Ballard, Heather; Kilroy, Gail; Day, Britton C; Wang, Zhong Q; Ribnicky, David M; Cefalu, William T; Floyd, Z Elizabeth

    2014-01-01

    Obesity is linked to insulin resistance, a primary component of metabolic syndrome and type 2 diabetes. The problem of obesity-related insulin resistance is compounded when age-related skeletal muscle loss, called sarcopenia, occurs with obesity. Skeletal muscle loss results from elevated levels of protein degradation and prevention of obesity-related sarcopenic muscle loss will depend on strategies that target pathways involved in protein degradation. An extract from Artemisia dracunculus, termed PMI 5011, improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance. The aim of this study was to examine the effect of PMI 5011 on the ubiquitin-proteasome system, a central regulator of muscle protein degradation. Gastrocnemius and vastus lateralis skeletal muscle was obtained from KK-A(y) obese diabetic mice fed a control or 1% (w/w) PMI 5011-supplemented diet. Regulation of genes encoding enzymes of the ubiquitin-proteasome system was determined using real-time quantitative reverse transcriptase polymerase chain reaction. Although MuRF-1 ubiquitin ligase gene expression is consistently down-regulated in skeletal muscle, atrogin-1, Fbxo40, and Traf6 expression is differentially regulated by PMI 5011. Genes encoding other enzymes of the ubiquitin-proteasome system ranging from ubiquitin to ubiquitin-specific proteases are also regulated by PMI 5011. Additionally, expression of the gene encoding the microtubule-associated protein-1 light chain 3 (LC3), a ubiquitin-like protein pivotal to autophagy-mediated protein degradation, is down-regulated by PMI 5011 in the vastus lateralis. PMI 5011 alters the gene expression of ubiquitin-proteasome system enzymes that are essential regulators of skeletal muscle mass. This suggests that PMI 5011 has therapeutic potential in the treatment of obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation. Copyright © 2014 Elsevier Inc

  15. Relative Skeletal Muscle Mass Is Associated with Development of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Byung Sam Park

    2013-12-01

    Full Text Available BackgroundVisceral adiposity is related to insulin resistance. Skeletal muscle plays a central role in insulin-mediated glucose disposal; however, little is known about the association between muscle mass and metabolic syndrome (MS. This study is to clarify the clinical role of skeletal muscle mass in development of MS.MethodsA total of 1,042 subjects were enrolled. Subjects with prior MS and chronic diseases were excluded. After 24 months, development of MS was assessed using NCEP-ATP III criteria. Skeletal muscle mass (SMM; kg, body fat mass (BFM; kg, and visceral fat area (VFA; cm2 were obtained from bioelectrical analysis. Then, the following values were calculated as follows: percent of SMM (SMM%; %: SMM (kg/weight (kg, skeletal muscle index (SMI; kg/m2: SMM (kg/height (m2, skeletal muscle to body fat ratio (MFR: SMM (kg/BFM (kg, and skeletal muscle to visceral fat ratio (SVR; kg/cm2: SMM (kg/VFA (cm2.ResultsAmong 838 subjects, 88 (10.5% were newly diagnosed with MS. Development of MS increased according to increasing quintiles of BMI, SMM, VFA, and SMI, but was negatively associated with SMM%, MFR, and SVR. VFA was positively associated with high waist circumference (WC, high blood pressure (BP, dysglycemia, and high triglyceride (TG. In contrast, MFR was negatively associated with high WC, high BP, dysglycemia, and high TG. SVR was negatively associated with all components of MS.ConclusionRelative SMM ratio to body composition, rather than absolute mass, may play a critical role in development of MS and could be used as a strong predictor.

  16. Muscle mass as a target to reduce fatigue in patients with advanced cancer.

    Science.gov (United States)

    Neefjes, Elisabeth C W; van den Hurk, Renske M; Blauwhoff-Buskermolen, Susanne; van der Vorst, Maurice J D L; Becker-Commissaris, Annemarie; de van der Schueren, Marian A E; Buffart, Laurien M; Verheul, Henk M W

    2017-08-01

    Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF. A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B - 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found (n = 82). The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  17. Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.

    Directory of Open Access Journals (Sweden)

    Ghulam Hussain

    Full Text Available The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS. Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

  18. Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Grunnet, Louise G; Nilsson, Emma; Ling, Charlotte

    2009-01-01

    Objective. Common variants in FTO (the fat-mass and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and non-genetic regulation of FTO mRNA in skeletal muscle...... and adipose tissue, and their influence on in vivo glucose and fat metabolism. Research Design and Methods. The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years......) and elderly (58-66 years) non-diabetic twins examined by a hyperinsulinemic euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n=226) and skeletal muscle biopsies (n=158). Results. Heritability of FTO expression in both tissues was low, and FTO...

  19. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK.

    Science.gov (United States)

    Merry, Troy L; Steinberg, Gregory R; Lynch, Gordon S; McConell, Glenn K

    2010-03-01

    Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPKalpha2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-l-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). Contraction increased AMPKalpha2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and l-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and l-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPKalpha Thr(172) phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or l-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.

  20. Correlates of increased lean muscle mass in women with polycystic ovary syndrome.

    Science.gov (United States)

    Carmina, E; Guastella, E; Longo, R A; Rini, G B; Lobo, R A

    2009-10-01

    Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed. Prospective investigation. Ninety-five women with PCOS were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT were determined. Free androgen index (FAI) and insulin resistance (by QUICKI) were calculated. In PCOS, waist circumference and insulin were higher and QUICKI lower than in controls (Plean mass were higher in PCOS compared to controls (PPCOS (PPCOS patients had abnormal (> or = 0.9 mm) values. Lean mass correlated with fat parameters, insulin, QUICKI, and FAI, but not with total testosterone; and after adjustments for insulin and QUICKI, lean mass still correlated with fat mass (PLean mass correlated with IMT (Plean mass independently of insulin. Bone mass correlated with lean and fat mass, but not with insulin or androgen. PCOS patients with 'pathological' IMT values had higher % trunk fat, lean mass, and insulin, lower QUICKI, and higher testosterone and FAI compared with those with normal IMT. Lean mass is increased in PCOS, while bone mass is similar to that of matched controls. The major correlates of lean mass are fat mass and insulin but not androgen. Lean mass also correlated with IMT, and although influenced by insulin, small changes in IMT may partially reflect changes in muscle mass, while clearly abnormal values relate to more severe abnormalities of PCOS.

  1. Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men.

    Science.gov (United States)

    Sjögren, Klara; Leung, Kin-Chuen; Kaplan, Warren; Gardiner-Garden, Margaret; Gibney, James; Ho, Ken K Y

    2007-07-01

    Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences.

  2. Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young girls.

    Science.gov (United States)

    Vicente-Rodriguez, G; Dorado, C; Ara, I; Perez-Gomez, J; Olmedillas, H; Delgado-Guerra, S; Calbet, J A L

    2007-05-01

    We compared 35 prepubertal girls, 9 artistic gymnasts and 13 rhythmic gymnasts with 13 nonphysically active controls to study the effect of gymnastics on bone and muscle mass. Lean mass, bone mineral content and areal density were measured by dual energy X-ray absorptiometry, and physical fitness was also assessed. The artistic gymnasts showed a delay in pubertal development compared to the other groups (partistic gymnasts had a 16 and 17 % higher aerobic power and anaerobic capacity, while the rhythmic group had a 14 % higher anaerobic capacity than the controls, respectively (all partistic gymnasts had higher lean mass (partistic and the rhythmic gymnasts (partistic group compared to the other groups. Lean mass strongly correlated with bone mineral content (r=0.84, partistic gymnastic participation is associated with delayed pubertal development, enhanced physical fitness, muscle mass, and bone density in prepubertal girls, eliciting a higher osteogenic stimulus than rhythmic gymnastic.

  3. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

    Science.gov (United States)

    Fry, Christopher S.; Lee, Jonah D.; Jackson, Janna R.; Kirby, Tyler J.; Stasko, Shawn A.; Liu, Honglu; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

    2014-01-01

    Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

  4. Rac1 Is a Novel Regulator of Contraction-Stimulated Glucose Uptake in Skeletal Muscle

    Science.gov (United States)

    Sylow, Lykke; Jensen, Thomas E.; Kleinert, Maximilian; Mouatt, Joshua R.; Maarbjerg, Stine J.; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T.; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A.

    2013-01-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (∼60–100%) and humans (∼40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20–58% in extensor digitorum longus (EDL; P Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake. PMID:23274900

  5. Hormone-sensitive lipase (HSL) expression and regulation by epinephrine and exercise in skeletal muscle

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Stallknecht, Bente Merete; Donsmark, Morten

    2002-01-01

    Abstract Triacylglycerol (TG) is stored in lipid droplets in the cytoplasm of skeletal muscle. The energy content of the TG depot is higher than the energy content of the muscle glycogen depot. The enzymatic regulation of intracellular TG hydrolysis in skeletal muscle has not been elucidated...... in the presence of an anti-HSL antibody. The effect of epinephrine could be blocked by propanolol and mimicked by incubation of a crude supernatant from control muscle with the catalytic subunit of cAMP-dependent protein kinase. The effect of contractions was transient as TO activity declined to basal levels...... and contractions were partially additive. In rats training increased epinephrine-stimulated TO activity and HSL concentration in adipose tissue but not in muscle. In humans, at the end of 60 min of exercise muscle, TO activity was increased in healthy, but not in adrenalectomized, subjects. In conclusion, HSL...

  6. Rac1--a novel regulator of contraction-stimulated glucose uptake in skeletal muscle.

    Science.gov (United States)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

    2014-12-01

    Muscle contraction stimulates muscle glucose uptake by facilitating translocation of glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibres. The intracellular mechanisms regulating this process are not well understood. The GTPase Rac1 has, until recently, been investigated only with regard to its involvement in insulin-stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise and contraction-stimulated glucose uptake in skeletal muscle, because muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake. The molecular mechanism by which Rac1 regulates glucose uptake is presently unknown. However, recent studies link Rac1 to the actin cytoskeleton, the small GTPase RalA and/or free radical production, which have previously been shown to be regulators of glucose uptake in muscle. We propose a model in which Rac1 is activated by contraction- and exercise-induced mechanical stress signals and that Rac1 in conjunction with other signalling regulates glucose uptake during muscle contraction and exercise. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  7. The Effect of Antagonist Muscle Sensory Input on Force Regulation.

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

    Full Text Available The purpose of this study was to understand how stretch-related sensory feedback from an antagonist muscle affects agonist muscle output at different contraction levels in healthy adults. Ten young (25.3 ± 2.4 years, healthy subjects performed constant isometric knee flexion contractions (agonist at 6 torque levels: 5%, 10%, 15%, 20%, 30%, and 40% of their maximal voluntary contraction. For half of the trials, subjects received patellar tendon taps (antagonist sensory feedback during the contraction. We compared error in targeted knee flexion torque and hamstring muscle activity, with and without patellar tendon tapping, across the 6 torque levels. At lower torque levels (5%, 10%, and 15%, subjects produced greater knee torque error following tendon tapping compared with the same torque levels without tendon tapping. In contrast, we did not find any difference in torque output at higher target levels (20%, 30%, and 40% between trials with and without tendon tapping. We also observed a load-dependent increase in the magnitude of agonist muscle activity after tendon taps, with no associated load-dependent increase in agonist and antagonist co-activation, or reflex inhibition from the antagonist tapping. The findings suggest that at relatively low muscle activity there is a deficiency in the ability to correct motor output after sensory disturbances, and cortical centers (versus sub-cortical are likely involved.

  8. CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle.

    Science.gov (United States)

    Witczak, Carol A; Jessen, Niels; Warro, Daniel M; Toyoda, Taro; Fujii, Nobuharu; Anderson, Mark E; Hirshman, Michael F; Goodyear, Laurie J

    2010-06-01

    Studies using chemical inhibitors have suggested that the Ca(2+)-sensitive serine/threonine kinase Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of both insulin- and contraction-stimulated glucose uptake in skeletal muscle. However, due to nonspecificity of these inhibitors, the specific role that CaMKII may play in the regulation of glucose uptake is not known. We sought to determine whether specific inhibition of CaMKII impairs insulin- and/or contraction-induced glucose uptake in mouse skeletal muscle. Expression vectors containing green fluorescent protein conjugated to a CaMKII inhibitory (KKALHRQEAVDCL) or control (KKALHAQERVDCL) peptide were transfected into tibialis anterior muscles by in vivo electroporation. After 1 wk, muscles were assessed for peptide expression, CaMK activity, insulin- and contraction-induced 2-[(3)H]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins. Expression of the CaMKII inhibitory peptide decreased muscle CaMK activity approximately 35% compared with control peptide. Insulin-induced glucose uptake was not changed in muscles expressing the inhibitory peptide. In contrast, expression of the inhibitory peptide significantly decreased contraction-induced muscle glucose uptake (approximately 30%). Contraction-induced decreases in muscle glycogen were not altered by the inhibitory peptide. The CaMKII inhibitory peptide did not alter expression of the glucose transporter GLUT4 and did not impair contraction-induced increases in the phosphorylation of AMP-activated protein kinase (Thr(172)) or TBC1D1/TBC1D4 on phospho-Akt substrate sites. These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle. However, CaMKII plays a critical role in the regulation of contraction-induced glucose uptake in mouse skeletal muscle.

  9. Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation During Muscle Regeneration.

    Science.gov (United States)

    Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So-Ichiro; Okano, Hideyuki; Takeda, Shin'ichi; Akazawa, Chihiro

    2015-10-01

    Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin-4 (Ten-4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten-4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten-4-deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten-4-deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten-4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten-4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. © 2015 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  10. Muscle Satellite Cell Protein Teneurin‐4 Regulates Differentiation During Muscle Regeneration

    Science.gov (United States)

    Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So‐ichiro; Okano, Hideyuki; Takeda, Shin'ichi

    2015-01-01

    Abstract Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin‐4 (Ten‐4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten‐4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten‐4‐deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten‐4‐deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten‐4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten‐4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. Stem Cells 2015;33:3017–3027 PMID:26013034

  11. Psoas Muscle Cross-sectional Area as a Measure of Whole-body Lean Muscle Mass in Maintenance Hemodialysis Patients.

    Science.gov (United States)

    Morrell, Glen R; Ikizler, Talat A; Chen, Xiaorui; Heilbrun, Marta E; Wei, Guo; Boucher, Robert; Beddhu, Srinivasan

    2016-07-01

    We investigate whether psoas or paraspinous muscle area measured on a single L4-L5 image is a useful measure of whole lean body mass (LBM) compared to dedicated midthigh magnetic resonance imaging (MRI). Observational study. Outpatient dialysis units and a research clinic. One hundred five adult participants on maintenance hemodialysis. No control group was used. Psoas muscle area, paraspinous muscle area, and midthigh muscle area (MTMA) were measured by magnetic resonance imaging. LBM was measured by dual-energy absorptiometry scan. In separate multivariable linear regression models, psoas, paraspinous, and MTMA were associated with increase in LBM. In separate multivariate logistic regression models, C statistics for diagnosis of sarcopenia (defined as <25th percentile of LBM) were 0.69 for paraspinous muscle area, 0.81 for psoas muscle area, and 0.89 for MTMA. With sarcopenia defined as <10th percentile of LBM, the corresponding C statistics were 0.71, 0.92, and 0.94. We conclude that psoas muscle area provides a good measure of whole-body muscle mass, better than paraspinous muscle area but slightly inferior to midthigh measurement. Hence, in body composition studies a single axial MR image at the L4-L5 level can be used to provide information on both fat and muscle and may eliminate the need for time-consuming measurement of muscle area in the thigh. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  12. Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle.

    Science.gov (United States)

    Chao, Lily C; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F

    2007-09-01

    Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared with oxidative muscle and is responsive to beta-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including glucose transporter 4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including glucose transporter 4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by small hairpin RNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple genes involved in glucose metabolism in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression.

  13. Strain in shock-loaded skeletal muscle and the time scale of muscular wobbling mass dynamics.

    Science.gov (United States)

    Christensen, Kasper B; Günther, Michael; Schmitt, Syn; Siebert, Tobias

    2017-10-16

    In terrestrial locomotion, muscles undergo damped oscillations in response to limb impacts with the ground. Muscles are also actuators that generate mechanical power to allow locomotion. The corresponding elementary contractile process is the work stroke of an actin-myosin cross-bridge, which may be forcibly detached by superposed oscillations. By experimentally emulating rat leg impacts, we found that full activity and non-fatigue must meet to possibly prevent forcible cross-bridge detachment. Because submaximal muscle force represents the ordinary locomotor condition, our results show that forcible, eccentric cross-bridge detachment is a common, physiological process even during isometric muscle contractions. We also calculated the stiffnesses of the whole muscle-tendon complex and the fibre material separately, as well as Young's modulus of the latter: 1.8 MPa and 0.75 MPa for fresh, fully active and passive fibres, respectively. Our inferred Young's modulus of the tendon-aponeurosis complex suggests that stiffness in series to the fibre material is determined by the elastic properties of the aponeurosis region, rather than the tendon material. Knowing these stiffnesses and the muscle mass, the complex' eigenfrequency for responses to impacts can be quantified, as well as the size-dependency of this time scale of muscular wobbling mass dynamics.

  14. Vasodilator interactions in skeletal muscle blood flow regulation

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Nyberg, Michael Permin; Jensen, Lasse Gliemann

    2012-01-01

    During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or the extraluminal side of the blood vessels. A number...... vasodilators are both stimulated by several compounds, eg. adenosine, ATP, acetylcholine, bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other...... is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperemic response remains unexplained. It is plausible...

  15. Vascular Function and Regulation of Blood Flow in Resting and Contracting Skeletal Muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin

    importance. The present work provides new insight in to vasodilator interactions important for exercise hyperemia and sheds light on mechanisms important for vascular function and regulation of skeletal muscle blood flow in essential hypertension (high blood pressure) and aging and identifies mechanisms......The precise matching of blood flow, oxygen delivery and metabolism is essential as it ensures that any increase in muscle work is precisely matched by increases in oxygen delivery. Therefore, understanding the control mechanisms of skeletal muscle blood flow regulation is of great biological...... in the regulation of exercise hyperemia. Furthermore, blood flow to contracting leg skeletal muscles is reduced both in essential hypertension and with aging. The potential difference in vasoactive system(s) responsible for the reduction in blood flow in the two conditions is in agreement with the suggestion...

  16. Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Esther Barreiro

    2016-05-01

    Full Text Available Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF, chronic obstructive pulmonary disease (COPD, cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of key cellular molecules such as proteins, DNA, and lipids, leading to cellular injury and death. Protein oxidation including protein carbonylation was demonstrated to modify enzyme activity and DNA binding of transcription factors, while also rendering proteins more prone to proteolytic degradation. Given the relevance of protein oxidation in the pathophysiology of many chronic conditions and their comorbidities, the current review focuses on the analysis of different studies in which the biological and clinical significance of the modifications induced by reactive carbonyls on proteins have been explored so far in skeletal muscles of patients and animal models of chronic conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and physiological aging. Future research will elucidate the specific impact and sites of reactive carbonyls on muscle protein content and function in human conditions.

  17. Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice.

    Science.gov (United States)

    Camporez, João-Paulo G; Petersen, Max C; Abudukadier, Abulizi; Moreira, Gabriela V; Jurczak, Michael J; Friedman, Glenn; Haqq, Christopher M; Petersen, Kitt Falk; Shulman, Gerald I

    2016-02-23

    Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.

  18. Skeletal muscle gene expression in response to resistance exercise: sex specific regulation

    Directory of Open Access Journals (Sweden)

    Burant Charles F

    2010-11-01

    Full Text Available Abstract Background The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE, might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise or late recovery (24 h post-exercise time point. Muscle transcription profiles were compared in the resting state between men (n = 6 and women (n = 8, and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females. A logistic regression-based method (LRpath, following Bayesian moderated t-statistic (IMBT, was used to test gene functional groups and biological pathways enriched with differentially expressed genes. Results This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females

  19. Tissue Selective Androgen Receptor Modulators (SARMs) Increase Pelvic Floor Muscle Mass in Ovariectomized Mice.

    Science.gov (United States)

    Ponnusamy, Suriyan; Sullivan, Ryan D; Thiyagarajan, Thirumagal; Tillmann, Heather; Getzenberg, Robert H; Narayanan, Ramesh

    2017-03-01

    Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including selective androgen receptor modulators (SARMs) may serve as therapeutic options for individuals with SUI. In this study, two SARMs (GTx-024 and GTx-027) were evaluated in a post-menopausal animal model in order to determine their effect on pelvic floor muscles. Female C57BL/6 mice were ovariectomized and their pelvic muscles allowed to regress. The animals were then treated with vehicle or doses of GTx-024 or GTx-027. Animal total body weight, lean body mass, and pelvic floor muscle weights were measured along with the expression of genes associated with muscle catabolism. Treatment with the SARMs resulted in a restoration of the pelvic muscles to the sham-operated weight. Coordinately, the induction of genes associated with muscle catabolism was inhibited. Although a trend was observed towards an increase in total lean body mass in the SARM-treated groups, no significant differences were detected. Treatment of an ovariectomized mouse model with SARMs resulted in an increase in pelvic floor muscles, which may translate to an improvement of symptoms associated with SUI and serves as the basis for evaluating their clinical use. J. Cell. Biochem. 118: 640-646, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

    Science.gov (United States)

    Kindler, J M; Pollock, N K; Laing, E M; Jenkins, N T; Oshri, A; Isales, C; Hamrick, M; Lewis, R D

    2016-01-01

    IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

  1. Loss of mass and performance in skeletal muscle tissue: a continuum model

    Directory of Open Access Journals (Sweden)

    Giantesio Giulia

    2018-02-01

    Full Text Available We present a continuum hyperelastic model which describes the mechanical response of a skeletal muscle tissue when its strength and mass are reduced by aging. Such a reduction is typical of a geriatric syndrome called sarcopenia. The passive behavior of the material is described by a hyperelastic, polyconvex, transversely isotropic strain energy function, and the activation of the muscle is modeled by the so called active strain approach. The loss of ability of activating of an elder muscle is then obtained by lowering of some percentage the active part of the stress, while the loss of mass is modeled through a multiplicative decomposition of the deformation gradient. The obtained stress-strain relations are graphically represented and discussed in order to study some of the effects of sarcopenia.

  2. Premature loss of muscle mass and function in type 2 diabetes.

    Science.gov (United States)

    Guerrero, N; Bunout, D; Hirsch, S; Barrera, G; Leiva, L; Henríquez, S; De la Maza, M P

    2016-07-01

    Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. To study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but

  3. Airway smooth muscle cells : regulators of airway inflammation

    NARCIS (Netherlands)

    Zuyderduyn, Suzanne

    2007-01-01

    Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this

  4. Altered mitochondrial regulation in quadriceps muscles of patients with COPD

    DEFF Research Database (Denmark)

    Naimi, Ashley I; Bourbeau, Jean; Perrault, Helene

    2011-01-01

    Evidence exists for locomotor muscle impairment in patients with chronic obstructive pulmonary disease (COPD), including fiber type alterations and reduced mitochondrial oxidative capacity. In this study high-resolution respirometry was used to quantify oxygen flux in permeabilized fibres from bi...

  5. Factors regulating fat oxidation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiens, Bente; Alsted, Thomas Junker; Jeppesen, Jacob

    2011-01-01

    In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin...

  6. Abelson tyrosine-protein kinase 2 regulates myoblast proliferation and controls muscle fiber length

    Science.gov (United States)

    Lee, Jennifer K; Hallock, Peter T

    2017-01-01

    Muscle fiber length is nearly uniform within a muscle but widely different among different muscles. We show that Abelson tyrosine-protein kinase 2 (Abl2) has a key role in regulating myofiber length, as a loss of Abl2 leads to excessively long myofibers in the diaphragm, intercostal and levator auris muscles but not limb muscles. Increased myofiber length is caused by enhanced myoblast proliferation, expanding the pool of myoblasts and leading to increased myoblast fusion. Abl2 acts in myoblasts, but as a consequence of expansion of the diaphragm muscle, the diaphragm central tendon is reduced in size, likely contributing to reduced stamina of Abl2 mutant mice. Ectopic muscle islands, each composed of myofibers of uniform length and orientation, form within the central tendon of Abl2+/− mice. Specialized tendon cells, resembling tendon cells at myotendinous junctions, form at the ends of these muscle islands, suggesting that myofibers induce differentiation of tendon cells, which reciprocally regulate myofiber length and orientation. PMID:29231808

  7. Akirin1 (Mighty), a novel promyogenic factor regulates muscle regeneration and cell chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Salerno, Monica Senna; Dyer, Kelly; Bracegirdle, Jeremy; Platt, Leanne; Thomas, Mark; Siriett, Victoria [Functional Muscle Genomics, AgResearch, Hamilton (New Zealand); Kambadur, Ravi [Functional Muscle Genomics, AgResearch, Hamilton (New Zealand); School of Biological Sciences, Nanyang Technological University, Singapore (Singapore); Sharma, Mridula, E-mail: bchmridu@nus.edu.sg [Functional Muscle Genomics, AgResearch, Hamilton (New Zealand)

    2009-07-15

    Akirin1 (Mighty) is a downstream target gene of myostatin and has been shown to be a promyogenic factor. Although expressed in many tissues, akirin1 is negatively regulated by myostatin specifically in skeletal muscle tissue. In this manuscript we have characterized the possible function of akirin1 in postnatal muscle growth. Molecular and immunohistological analyses indicated that while low levels of akirin1 are associated with quiescent satellite cells (SC), higher levels of akirin1 are detected in activated proliferating SC indicating that akirin1 could be associated with satellite cell activation. In addition to SC, macrophages also express akirin1, and increased expression of akirin1 resulted in more efficient chemotaxis of both macrophages and myoblasts. Akirin1 appears to regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway. Expression analysis during muscle regeneration also indicated that akirin1 expression is detected very early (day 2) in regenerating muscle, and expression gradually peaks to coincide the nascent myotube formation stage of muscle regeneration. Based on these results we propose that akirin1 could be acting as a transducer of early signals of muscle regeneration. Thus, we speculate that myostatin regulates key steps of muscle regeneration including chemotaxis of inflammatory cells, SC activation and migration through akirin1.

  8. Akirin1 (Mighty), a novel promyogenic factor regulates muscle regeneration and cell chemotaxis

    International Nuclear Information System (INIS)

    Salerno, Monica Senna; Dyer, Kelly; Bracegirdle, Jeremy; Platt, Leanne; Thomas, Mark; Siriett, Victoria; Kambadur, Ravi; Sharma, Mridula

    2009-01-01

    Akirin1 (Mighty) is a downstream target gene of myostatin and has been shown to be a promyogenic factor. Although expressed in many tissues, akirin1 is negatively regulated by myostatin specifically in skeletal muscle tissue. In this manuscript we have characterized the possible function of akirin1 in postnatal muscle growth. Molecular and immunohistological analyses indicated that while low levels of akirin1 are associated with quiescent satellite cells (SC), higher levels of akirin1 are detected in activated proliferating SC indicating that akirin1 could be associated with satellite cell activation. In addition to SC, macrophages also express akirin1, and increased expression of akirin1 resulted in more efficient chemotaxis of both macrophages and myoblasts. Akirin1 appears to regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway. Expression analysis during muscle regeneration also indicated that akirin1 expression is detected very early (day 2) in regenerating muscle, and expression gradually peaks to coincide the nascent myotube formation stage of muscle regeneration. Based on these results we propose that akirin1 could be acting as a transducer of early signals of muscle regeneration. Thus, we speculate that myostatin regulates key steps of muscle regeneration including chemotaxis of inflammatory cells, SC activation and migration through akirin1.

  9. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth

    NARCIS (Netherlands)

    Van Der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    VAN DER HEIJDEN, G.-J., Z. J. WANG, Z. CHU, G. TOFFOLO, E. MANESSO, P. J. J. SAUER, and A. L. SUNEHAG. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth. Med. Sci. Sports Exerc., Vol. 42, No. 11, pp. 1973-1980, 2010. Introduction: Data on the metabolic effects of

  10. Postoperative loss of skeletal muscle mass, complications and quality of life in patients undergoing cardiac surgery

    NARCIS (Netherlands)

    van Venrooij, Lenny M. W.; Verberne, Hein J.; de Vos, Rien; Borgmeijer-Hoelen, Mieke M. M. J.; van Leeuwen, Paul A. M.; de Mol, Bas A. J. M.

    2012-01-01

    Objective: The objective of this study was to describe postoperative undernutrition in terms of postoperative losses of appendicular skeletal muscle mass (ASMM) with respect to complications, quality of life, readmission, and 1-y mortality after cardiac surgery. Methods: Patients undergoing cardiac

  11. Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

    NARCIS (Netherlands)

    Ide, K.; Pott, F.; van Lieshout, J. J.; Secher, N. H.

    1998-01-01

    We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus

  12. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth

    NARCIS (Netherlands)

    Van Der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    2010-01-01

    VAN DER HEIJDEN, G.-J., Z. J. WANG, Z. CHU, G. TOFFOLO, E. MANESSO, P. J. J. SAUER, and A. L. SUNEHAG. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth. Med. Sci. Sports Exerc., Vol. 42, No. 11, pp. 1973-1980, 2010. Introduction: Data on the metabolic effects of

  13. Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle function

    Science.gov (United States)

    Gallagher, Thomas L.; Arribere, Joshua A.; Geurts, Paul A.; Exner, Cameron R. T.; McDonald, Kent L.; Dill, Kariena K.; Marr, Henry L.; Adkar, Shaunak S.; Garnett, Aaron T.; Amacher, Sharon L.; Conboy, John G.

    2012-01-01

    Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos was strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle function. PMID:21925157

  14. Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions.

    Science.gov (United States)

    Gallagher, Thomas L; Arribere, Joshua A; Geurts, Paul A; Exner, Cameron R T; McDonald, Kent L; Dill, Kariena K; Marr, Henry L; Adkar, Shaunak S; Garnett, Aaron T; Amacher, Sharon L; Conboy, John G

    2011-11-15

    Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos were strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle functions. Published by Elsevier Inc.

  15. Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice

    Science.gov (United States)

    2006-07-01

    the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin...and rates of breast cancer initiation and progression. 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin , MPA, DMBA, Activin receptor 16...including interleukins, Insulin-like Growth Factor (IGF) isoforms, IGF-binding proteins and myostatin . To determine the effect of skeletal muscle mass

  16. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia) : the Longitudinal Aging Study Amsterdam

    NARCIS (Netherlands)

    Visser, Marjolein; Deeg, Dorly J H; Lips, Paul

    2003-01-01

    The age-related change in hormone concentrations has been hypothesized to play a role in the loss of muscle mass and muscle strength with aging, also called sarcopenia. The aim of this prospective study was to investigate whether low serum 25-hydroxyvitamin D (25-OHD) and high serum PTH

  17. Rho Kinase (ROCK) collaborates with Pak to Regulate Actin Polymerization and Contraction in Airway Smooth Muscle.

    Science.gov (United States)

    Zhang, Wenwu; Bhetwal, Bhupal P; Gunst, Susan J

    2018-05-10

    The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation. We find that ROCK regulates airway smooth muscle contraction by activating the serine-threonine kinase Pak, which mediates the activation of Cdc42 and Neuronal-Wiskott-Aldrich Syndrome protein (N-WASp). N-WASP transmits signals from cdc42 to the Arp2/3 complex for the nucleation of actin filaments. These results demonstrate a novel molecular function for ROCK in the regulation of Pak and cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle. Rho kinase (ROCK), a RhoA GTPase effector, can regulate the contraction of airway and other smooth muscle tissues. In some tissues, ROCK can inhibit myosin regulatory light chain (RLC) phosphatase, which increases the phosphorylation of myosin RLC and promotes smooth muscle contraction. ROCK can also regulate cell motility and migration by affecting F-actin dynamics. Actin polymerization is stimulated by contractile agonists in airway smooth muscle tissues and is required for contractile tension development in addition to myosin RLC phosphorylation. We investigated the mechanisms by which ROCK regulates the contractility of tracheal smooth muscle tissues by expressing a kinase inactive mutant of ROCK, ROCK-K121G, in the tissues or by treating them with the ROCK inhibitor, H-1152P. Our results show no role for ROCK in the regulation of non-muscle or smooth muscle myosin RLC phosphorylation during contractile stimulation in this tissue

  18. Age associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life

    Science.gov (United States)

    SUMMARY: This 3 year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of ...

  19. Pro-inflammatory capacity of classically activated monocytes relates positively to muscle mass and strength.

    Science.gov (United States)

    Beenakker, Karel G M; Westendorp, Rudi G J; de Craen, Anton J M; Slagboom, Pieternella E; van Heemst, Diana; Maier, Andrea B

    2013-08-01

    In mice, monocytes that exhibit a pro-inflammatory profile enter muscle tissue after muscle injury and are crucial for clearance of necrotic tissue and stimulation of muscle progenitor cell proliferation and differentiation. The aim of this study was to test if pro-inflammatory capacity of classically activated (M1) monocytes relates to muscle mass and strength in humans. This study included 191 male and 195 female subjects (mean age 64.2 years (SD 6.4) and 61.9 ± 6.4, respectively) of the Leiden Longevity Study. Pro-inflammatory capacity of M1 monocytes was assessed by ex vivo stimulation of whole blood with Toll-like receptor (TLR) 4 agonist lipopolysaccharide (LPS) and TLR-2/1 agonist tripalmitoyl-S-glycerylcysteine (Pam₃Cys-SK₄), both M1 phenotype activators. Cytokines that stimulate M1 monocyte response (IFN-γ and GM-CSF) as well as cytokines that are secreted by M1 monocytes (IL-6, TNF-α, IL-12, and IL-1β) were measured. Analyses were adjusted for age, height, and body fat mass. Upon stimulation with LPS, the cytokine production capacity of INF-γ, GM-CSF, and TNF-α was significantly positively associated with lean body mass, appendicular lean mass and handgrip strength in men, but not in women. Upon stimulation with Pam₃Cys-SK₄, IL-6; TNF-α; and Il-1β were significantly positively associated with lean body mass and appendicular lean in women, but not in men. Taken together, this study shows that higher pro-inflammatory capacity of M1 monocytes upon stimulation is associated with muscle characteristics and sex dependent. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

  20. Relationship between Handgrip Strength and Muscle Mass in Female Survivors of Breast Cancer: A Mediation Analysis.

    Science.gov (United States)

    Benavides-Rodríguez, Lorena; García-Hermoso, Antonio; Rodrigues-Bezerra, Diogo; Izquierdo, Mikel; Correa-Bautista, Jorge Enrique; Ramírez-Vélez, Robinson

    2017-07-04

    This study explored the mediating factors of sarcopenia in a group of women survivors of breast cancer in Bogotá, Colombia. This was a descriptive cross-sectional study with 98 women survivors of breast cancer, who were registered with the SIMMON (Integrated Synergies to Improve Oncological Management in Colombia) Foundation. Body weight, height, and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Body composition (percentage of fat and muscle mass) was evaluated via four-pole bioelectrical impedance analysis. Sarcopenia was defined as low muscle mass plus low grip strength or low gait speed (European Working Group on Sarcopenia in Older People (EWGSOP) criteria). A "causal" mediation analysis with the Baron & Kenny procedure (PROCESS ® macro, Columbus, OH, USA) was used to explore variables related to sarcopenia. Analyses were performed with the IBM SPSS 21 statistical package (SPSS Inc., Chicago, IL, USA). The significance level of the results obtained in the hypothesis contrast was p < 0.05. The mean age of the sample was 65.5 ± 5.9 years, with a BMI of 27.8 ± 4.7 kg/m². The prevalence of sarcopenia was 22.4%. Linear regression models suggest a partial mediation of anthropometric parameters (body mass, body mass index and waist circumference) in the association between handgrip strength and muscle mass. In conclusion, one in every five women survivors of breast cancer had sarcopenia. The findings seem to emphasize the importance of obesity prevention in women survivors of breast cancer, suggesting that high handgrip strength may not relate closely to greater muscle mass and therefore would not exclude the risk of sarcopenia.

  1. Regulation of human skeletal muscle perfusion and its heterogeneity during exercise in moderate hypoxia

    DEFF Research Database (Denmark)

    Heinonen, Ilkka H; Kemppainen, Jukka; Kaskinoro, Kimmo

    2010-01-01

    , the results show that increased BF during one-leg exercise in moderate hypoxia is confined only to the contracting muscles, and the working muscle hyperemia appears not to be directly mediated by adenosine. Increased flow heterogeneity in noncontracting muscles likely reflects sympathetic nervous constraints...... healthy young men using positron emission tomography during one-leg dynamic knee extension exercise in normoxia and moderate physiological systemic hypoxia (14% O(2) corresponding to approximately 3,400 m of altitude) without and with local adenosine receptor inhibition with femoral artery infusion...... to curtail BF increments in areas other than working skeletal muscles, but this effect is not potentiated in moderate systemic hypoxia during small muscle mass exercise....

  2. The giant protein titin regulates the length of the striated muscle thick filament.

    Science.gov (United States)

    Tonino, Paola; Kiss, Balazs; Strom, Josh; Methawasin, Mei; Smith, John E; Kolb, Justin; Labeit, Siegfried; Granzier, Henk

    2017-10-19

    The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin's C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health.

  3. Hormone-sensitive lipase (HSL) expression and regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Langfort, J; Ploug, T; Ihlemann, J

    1998-01-01

    Because the enzymatic regulation of muscle triglyceride metabolism is poorly understood we explored the character and activation of neutral lipase in muscle. Western blotting of isolated rat muscle fibers demonstrated expression of hormone-sensitive lipase (HSL). In incubated soleus muscle...... epinephrine increased neutral lipase activity by beta-adrenergic mechanisms involving cyclic AMP-dependent protein kinase (PKA). The increase was paralleled by an increase in glycogen phosphorylase activity and could be abolished by antiserum against HSL. Electrical stimulation caused a transient increase...... in activity of both neutral lipase and glycogen phosphorylase. The increase in lipase activity during contractions was not influenced by sympathectomy or propranolol. Training diminished the epinephrine induced lipase activation in muscle but enhanced the activation as well as the overall concentration...

  4. Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression

    OpenAIRE

    Goljanek-Whysall, Katarzyna; Iwanejko, Lesley A.; Vasilaki, Aphrodite; Pekovic-Vaughan, Vanja; McDonagh, Brian

    2016-01-01

    Ageing is associated with a progressive loss of skeletal muscle mass, quality and function?sarcopenia, associated with reduced independence and quality of life in older generations. A better understanding of the mechanisms, both genetic and epigenetic, underlying this process would help develop therapeutic interventions to prevent, slow down or reverse muscle wasting associated with ageing. Currently, exercise is the only known effective intervention to delay the progression of sarcopenia. Th...

  5. Regulation of PDH in human arm and leg muscles at rest and during intense exercise

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Birk, Jesper Bratz; Damsgaard, Rasmus

    2008-01-01

    To test the hypothesis that pyruvate dehydrogenase (PDH) is differentially regulated in specific human muscles, regulation of PDH was examined in triceps, deltoid, and vastus lateralis at rest and during intense exercise. To elicit considerable glycogen use, subjects performed 30 min of exhaustive...... arm cycling on two occasions and leg cycling exercise on a third day. Muscle biopsies were obtained from deltoid or triceps on the arm exercise days and from vastus lateralis on the leg cycling day. Resting PDH protein content and phosphorylation on PDH-E1 alpha sites 1 and 2 were higher (P ....05) in vastus lateralis than in triceps and deltoid as was the activity of oxidative enzymes. Net muscle glycogen utilization was similar in vastus lateralis and triceps ( approximately 50%) but less in deltoid (likely reflecting less recruitment of deltoid), while muscle lactate accumulation was approximately...

  6. Global gene expression in muscle from fasted/refed trout reveals up-regulation of genes promoting myofibre hypertrophy but not myofibre production.

    Science.gov (United States)

    Rescan, Pierre-Yves; Le Cam, Aurelie; Rallière, Cécile; Montfort, Jérôme

    2017-06-07

    , occurs in trout after refeeding. The generation of a large set of genes up-regulated in muscle of refed trout may yield insights into the molecular and cellular mechanisms controlling skeletal muscle mass in teleost and serve as a useful list of potential molecular markers of muscle growth in fish.

  7. Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle

    OpenAIRE

    Chao, Lily C.; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F.

    2007-01-01

    Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared to oxidativ...

  8. Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study.

    Science.gov (United States)

    Abramowitz, Matthew K; Hall, Charles B; Amodu, Afolarin; Sharma, Deep; Androga, Lagu; Hawkins, Meredith

    2018-01-01

    The level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has directly examined the effect of muscle mass on the BMI-mortality relationship. Body composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999-2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality. At any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30-40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity. Muscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.

  9. Myogenin regulates exercise capacity and skeletal muscle metabolism in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Jesse M Flynn

    2010-10-01

    Full Text Available Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

  10. Role of AMPK in Regulating Muscle Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus

    The ability of insulin to stimulate skeletal muscle glucose uptake is instrumental for controlling whole-body glucose homeostasis. Decreased peripheral sensitivity to insulin increases the risk of developing type 2 diabetes. Insulin sensitivity can be defined as the concentration of insulin that ...... prevail in healthy lean subjects. In the present thesis, experimental results from the three studies as well as unpublished observations are placed in the context of existing literature in order to provide a general overview of the current understandings within this field of research....

  11. Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

    Science.gov (United States)

    Nishida, Hikaru; Ikegami, Ayaka; Kaneko, Chiaki; Kakuma, Hitomi; Nishi, Hisano; Tanaka, Noriko; Aoyama, Michiko; Usami, Makoto; Okimura, Yasuhiko

    2015-01-01

    Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR) mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

  12. Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

    Directory of Open Access Journals (Sweden)

    Hikaru Nishida

    Full Text Available Branched-chain amino acids (BCAAs and IGF-I, the secretion of which is stimulated by growth hormone (GH, prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs. Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

  13. Protein needs in athletes and dietary-nutrition guidelines to gain muscle mass

    Directory of Open Access Journals (Sweden)

    Aritz Urdampilleta

    2014-05-01

    Full Text Available One of the most important effects of strength training is muscular hypertrophy. Athletes should optimize their nutritional management in order to compensate their own genetic limitations. The aim of this review is to analyze the scientific evidence concerning protein intake as a tool to achieve muscle hypertrophy. Depending on the expenditure and energy intake of athlete, a daily protein ranging between 10-15% of total dietary intake is needed. However in sports diets, it is preferable to estimate the amount of protein needed per kilogram of body weight in each individual. In this regard athletes should ingest an amount between 1.2 g and 1.8 g of proteins/kg of body mass/day to maintain their lean mass. In order to increase muscle mass (0.5 kg/week, athletes should take between 1.6 g and 1.8 g of protein/kg/day with an increase of 400-500 kcal in their daily diet. These needs will depend on the sport, muscular catabolic status, the athlete’s lean mass and glycogen stores. Protein needs will increase if muscle and liver glycogen stores are empty. Excess of protein intake (more than 2 g/kg/day, with full glycogen stores, does not benefit the athlete and could cause an increase in circulating ketones and urea, thereby producing an early dehydration.

  14. Impact of fat mass distribution body shapes on muscles strength and the joints pain

    Directory of Open Access Journals (Sweden)

    Zerf Mohammed

    2016-01-01

    Full Text Available Our study focuses on fat mass distribution body shapes type as measured to determine their effect on skeletal muscle strengthening lumbar extensors (upper and lower limbs where our background confirms that every girl has a natural body type of rectangle, apple, pear, or hourglass. It is good for her to know which type of body shape she is, so she can learn what exercises to do, whereas similar studies suggest that it is much better to challenge weight problems with exercise and dietary measures before resorting to figure shaping. For this purpose, our study was carried out with a total of thirty students, females listed in the Institute of Physical Education and Sport, University of Mostaganem, aged between 20 and 23 years; their homogeneity was based on age, sex, and academic specialty, classified based on the body mass index (BMI into two groups (normal and overweight and based on their body shape′s type into three groups (9 pear shape, 10 rectangle shape, and 11 hourglass shape as a protocol experimental to examine the impact of fat mass distribution body shapes type on lumbar extensor strength. Based on our data analysis, we confirm that the pear and the rectangle shape affect the strength lumbar extensors due to body weight distribution which increases the risks relating to the skeletal muscles. Weight gain is a factor contributing to the weakness of skeletal muscles. However, the body shape explains the anomalies of the distribution of fat mass and BMI risk observed in our sample in the lower and upper part of the body recorded by the values of Killy test and endurance of trunk, the case of the pear and the rectangle shape back pain, which are consisting in excess of the body fat distributed in comparison with less percentage of muscle mass. Whereas this difference can affect the pelvic position.

  15. Tetracycline-inducible system for regulation of skeletal muscle-specific gene expression in transgenic mice

    Science.gov (United States)

    Grill, Mischala A.; Bales, Mark A.; Fought, Amber N.; Rosburg, Kristopher C.; Munger, Stephanie J.; Antin, Parker B.

    2003-01-01

    Tightly regulated control of over-expression is often necessary to study one aspect or time point of gene function and, in transgenesis, may help to avoid lethal effects and complications caused by ubiquitous over-expression. We have utilized the benefits of an optimized tet-on system and a modified muscle creatine kinase (MCK) promoter to generate a skeletal muscle-specific, doxycycline (Dox) controlled over-expression system in transgenic mice. A DNA construct was generated in which the codon optimized reverse tetracycline transactivator (rtTA) was placed under control of a skeletal muscle-specific version of the mouse MCK promoter. Transgenic mice containing this construct expressed rtTA almost exclusively in skeletal muscles. These mice were crossed to a second transgenic line containing a bi-directional promoter centered on a tet responder element driving both a luciferase reporter gene and a tagged gene of interest; in this case the calpain inhibitor calpastatin. Compound hemizygous mice showed high level, Dox dependent muscle-specific luciferase activity often exceeding 10,000-fold over non-muscle tissues of the same mouse. Western and immunocytochemical analysis demonstrated similar Dox dependent muscle-specific induction of the tagged calpastatin protein. These findings demonstrate the effectiveness and flexibility of the tet-on system to provide a tightly regulated over-expression system in adult skeletal muscle. The MCKrtTA transgenic lines can be combined with other transgenic responder lines for skeletal muscle-specific over-expression of any target gene of interest.

  16. Extracellular creatine regulates creatine transport in rat and human muscle cells.

    OpenAIRE

    Loike, J D; Zalutsky, D L; Kaback, E; Miranda, A F; Silverstein, S C

    1988-01-01

    Muscle cells do not synthesize creatine; they take up exogenous creatine by specific Na+-dependent plasma membrane transporters. We found that extracellular creatine regulates the level of expression of these creatine transporters in L6 rat muscle cells. L6 myoblasts maintained for 24 hr in medium containing 1 mM creatine exhibited 1/3rd of the creatine transport activity of cells maintained for 24 hr in medium without creatine. Down-regulation of creatine transport was partially reversed whe...

  17. Regulation of pH in human skeletal muscle: adaptations to physical activity

    DEFF Research Database (Denmark)

    Juel, C

    2008-01-01

    -transport) and describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....... resonance technique to exercise experiments including blood sampling and muscle biopsies. The present review characterizes the cellular buffering system as well as the most important membrane transport systems involved (Na(+)/H(+) exchange, Na-bicarbonate co-transport and lactate/H(+) co...

  18. Ultrasonographic evaluation of the calf muscle mass and architecture in elderly patients with and without sarcopenia.

    Science.gov (United States)

    Kuyumcu, Mehmet Emin; Halil, Meltem; Kara, Özgür; Çuni, Bledjan; Çağlayan, Gökhan; Güven, Serdar; Yeşil, Yusuf; Arık, Güneş; Yavuz, Burcu Balam; Cankurtaran, Mustafa; Özçakar, Levent

    2016-01-01

    To sonographically assess the muscle mass and architecture of sarcopenic elderly subjects, and to explore the utility of ultrasound (US) measurements in predicting sarcopenia. One hundred elderly subjects were enrolled in this cross-sectional study. Mean age value of our study population was 73.08±6.18years. The diagnosis of sarcopenia was confirmed by measuring fat-free mass index (using bioelectrical impedance analysis) and handgrip strength. Calf circumference was measured and US evaluations comprised bilateral gastrocnemius muscle (MG) thickness, fascicle length and pennate angles; subcutaneous fat and dermis thicknesses in the calf. Bilateral muscle thickness and fascicle length values were significantly lower in patients with sarcopenia (both psarcopenia (all values>76.92%). Gastrocnemius muscle thickness and fascicle length values are lower in sarcopenic elderly and these two parameters can serve as alternative measurements for predicting/quantifying sarcopenia. Calf circumference measurements alone may not be appropriate for assessing sarcopenia. Instead, US imaging can conveniently be used to evaluate different compartments of the musculoskelal system in (sarcopenic) elderly. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Regulation of Skeletal Muscle Plasticity by Protein Arginine Methyltransferases and Their Potential Roles in Neuromuscular Disorders

    Directory of Open Access Journals (Sweden)

    Derek W. Stouth

    2017-11-01

    Full Text Available Protein arginine methyltransferases (PRMTs are a family of enzymes that catalyze the methylation of arginine residues on target proteins, thereby mediating a diverse set of intracellular functions that are indispensable for survival. Indeed, full-body knockouts of specific PRMTs are lethal and PRMT dysregulation has been implicated in the most prevalent chronic disorders, such as cancers and cardiovascular disease (CVD. PRMTs are now emerging as important mediators of skeletal muscle phenotype and plasticity. Since their first description in muscle in 2002, a number of studies employing wide varieties of experimental models support the hypothesis that PRMTs regulate multiple aspects of skeletal muscle biology, including development and regeneration, glucose metabolism, as well as oxidative metabolism. Furthermore, investigations in non-muscle cell types strongly suggest that proteins, such as peroxisome proliferator-activated receptor-γ coactivator-1α, E2F transcription factor 1, receptor interacting protein 140, and the tumor suppressor protein p53, are putative downstream targets of PRMTs that regulate muscle phenotype determination and remodeling. Recent studies demonstrating that PRMT function is dysregulated in Duchenne muscular dystrophy (DMD, spinal muscular atrophy (SMA, and amyotrophic lateral sclerosis (ALS suggests that altering PRMT expression and/or activity may have therapeutic value for neuromuscular disorders (NMDs. This review summarizes our understanding of PRMT biology in skeletal muscle, and identifies uncharted areas that warrant further investigation in this rapidly expanding field of research.

  20. Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats.

    Science.gov (United States)

    Shankaran, Mahalakshmi; Shearer, Todd W; Stimpson, Stephen A; Turner, Scott M; King, Chelsea; Wong, Po-Yin Anne; Shen, Ying; Turnbull, Philip S; Kramer, Fritz; Clifton, Lisa; Russell, Alan; Hellerstein, Marc K; Evans, William J

    2016-03-15

    Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167-201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated (r(2) = 0.90-0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM. Copyright © 2016 the American Physiological Society.

  1. F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.

    Science.gov (United States)

    Sukari, Ammar; Muqbil, Irfana; Mohammad, Ramzi M; Philip, Philip A; Azmi, Asfar S

    2016-02-01

    Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Skeletal Muscle and Liver Lipidomics and the Regulation of FAT/CD36

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting

    induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid content in the liver, but not in muscle...... that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver...... during isolated muscle contractions. On the contrary, previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT...

  3. mTORC2 Regulation of Muscle Metabolism and Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kleinert, Maximilian

    and skeletal muscle to take up blood glucose, ultimately lowering blood glucose levels. A hallmark of T2D is decreased organ sensitivity to the effects of the insulin. Therefore, an early event in the pathogenesis of T2D is an increase in insulin secretion in response to eating a meal, as more insulin....... In the absence of insulin, the majority of GLUT4 resides within the muscle. Conversely, insulin stimulation increases the muscle’s permeability to glucose, by triggering GLUT4 translocation to the plasma membrane. The effect of insulin on GLUT4 translocation is mediated by a chain of molecular signaling events...... that mTORC2 controls skeletal muscle glycolysis and lipid storage. In agreement, Ric mKO mice exhibited reduced muscle glycolytic flux, greater reliance on fat as an energy substrate, re-partitioning of lean to fat mass and higher intramyocellular triacylglycerol (IMTG) levels compared to Ric WT mice...

  4. miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle

    Directory of Open Access Journals (Sweden)

    Duo Zhang

    2016-07-01

    Full Text Available Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC. Short-term high-fat diet (HFD feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα, which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

  5. Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS study.

    Science.gov (United States)

    Szulc, Pawel; Duboeuf, François; Marchand, François; Delmas, Pierre D

    2004-08-01

    Aging-related sarcopenia is characterized by a loss of muscle mass and strength and increased fatigability. However, studies of its determinants in elderly men are scarce. We investigated risk factors for sarcopenia in a large cohort of men. We analyzed 845 men aged 45-85 y who belonged to the MINOS cohort. Lifestyle factors (physical activity, tobacco smoking, alcohol intake, caffeine intake) were evaluated by using a standardized questionnaire. Appendicular skeletal muscle mass (ASM) was estimated by using dual-energy X-ray absorptiometry. The relative appendicular skeletal muscle mass index (RASM) was calculated as ASM/body height(2.3). Apparent free testosterone concentration (AFTC) and free testosterone index (FTI) were calculated on the basis of concentrations of total testosterone and sex hormone-binding globulin. RASM decreased with age (r = -0.29, P values for AFTC, FTI, or 25-hydroxycholecalciferol [25(OH)D] were >2 SDs below the mean for young men had significantly lower RASM than did men with higher values. Men with sarcopenia, defined as the lowest quartile of RASM in the studied cohort (normal RASM, weighed significantly less, smoked more, and spent significantly less time on leisure-time activities. Sarcopenic men also had lower values for testosterone, AFTC, FTI, and 25(OH)D. In elderly men, low physical activity, tobacco smoking, thinness, low testosterone (AFTC and FTI), and decreased 25(OH)D concentrations are risk factors for sarcopenia.

  6. Depression Is Associated With Muscle Mass And Strength In Patients With End Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Young Rim Song

    2012-06-01

    Full Text Available Depression is the most common psychiatric complication in patients with end-stage renal disease (ESRD. Sarcopenia, defined as loss of muscle mass and strength, is expected to be associated with depression, because both are closely linked to physical inactivity and functional impairment. We investigated the association of sarcopenia with depression in patients with ESRD. A total of 115 patients undergoing hemodialysis (HD were included in this study. Muscle mass was assessed by lean tissue index (LTI using portable whole body bioimpedance spectroscopy, and muscle strength was measured with handgrip strength (HGS. Depression was defined as Beck Depression Inventory-II (BDI-II score ≥16. About 60% of prevalent HD patients had depression. Compared to subjects without depression, depressed patients had a higher prevalence of sarcopenia (45.5 vs. 8.2%, p<0.001 and significantly increased serum IL-6 and hs-CRP level. However, (prealbumin and body mass index (BMI failed to correlate with BDI-II. HGS and LTI had a consistent negative effect on BDI-II even after adjusting other parameters including inflammation. In multivariate analysis, lower , increased IL-6 and β2-microglobulin,and sarcopenia were significant predictors for depression; sarcopenia was most powerful [odds ratio 9.01, 95% CI 3.60-12.22, p=0.001]. In conclusion, the prevalence of sarcopenia and depression was considerably high and and the presence of sarcopenia was an important predictor for depression.

  7. Age- and gender-dependent values of skeletal muscle mass in healthy children and adolescents

    OpenAIRE

    Webber, Colin E.; Barr, Ronald D.

    2011-01-01

    Background Skeletal muscle mass (SMM) can be extracted from whole-body scans obtained by X-ray-based dual-photon absorptiometry (DXA). There is a need to establish expected age-dependent values for children and adolescents. Methods Appendicular lean tissue mass (ALM) was extracted from whole-body DXA scans in 140 healthy children and adolescents (68 females and 72 males). Whole-body SMM was calculated from ALM using equations developed by Kim et al. (Am J Clin Nutr 84:1014–1020, 2006). Age-de...

  8. Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish

    Directory of Open Access Journals (Sweden)

    Zizhen Yao

    2013-04-01

    The basic helix–loop–helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast-twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a−/− embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program.

  9. Measurement of Muscle Protein Fractional Synthetic Rate by Capillary Gas Chromatography/Combustion Isotope Ratio Mass Spectrometry

    OpenAIRE

    Yarasheski, Kevin E.; Smith, Kenneth; Rennie, Michael J.; Bier, Dennis M.

    1992-01-01

    The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuo...

  10. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

    Science.gov (United States)

    Pecorella, Shelly R H; Potter, Jennifer V F; Cherry, Anne D; Peacher, Dionne F; Welty-Wolf, Karen E; Moon, Richard E; Piantadosi, Claude A; Suliman, Hagir B

    2015-10-15

    The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity. Copyright © 2015 the American Physiological Society.

  11. Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases

    Science.gov (United States)

    Chacon-Cabrera, Alba; Lund-Palau, Helena; Gea, Joaquim; Barreiro, Esther

    2016-01-01

    Background Disuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization. Methods Body and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations), proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days) of non-invasive hindlimb immobilization (plastic splint, I cohorts) and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts) following a seven-day period of immobilization. Groups of control animals were also used. Results Compared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis. Conclusions A consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised. PMID

  12. Intermittent pneumatic compression regulates expression of nitric oxide synthases in skeletal muscles.

    Science.gov (United States)

    Tan, Xiangling; Qi, Wen-Ning; Gu, Xiaosong; Urbaniak, James R; Chen, Long-En

    2006-01-01

    This study investigated the effects of intermittent pneumatic compression (IPC) on expression of nitric oxide synthase (NOS) isoforms in compressed (anterior tibialis, AT) and uncompressed (cremaster muscles, CM) skeletal muscles. Following IPC application of 0.5, 1, and 5h on both legs of rats, the endothelial NOS (eNOS) mRNA expression was significantly up-regulated to 1.2-, 1.8, and 2.7-fold from normal, respectively, in both AT and CM, and protein expression increased more than 1.5-fold of normal at each time point. Similarly, neuronal NOS expression was up-regulated, but to a lesser degree. In contrast, inducible NOS expression was significantly and time-dependently down-regulated in both muscles. After IPC cessation, eNOS levels returned to normal in both AT and CM. The results confirm our hypothesis that IPC-induced vasodilation is mediated by regulating expression of NOS isoforms, in particular eNOS, in both compressed and uncompressed skeletal muscles. The results also suggest the importance of precisely characterizing expression of each NOS isoform in tissue pathophysiology.

  13. Effect of regional muscle location but not adiposity on mitochondrial biogenesis-regulating proteins

    DEFF Research Database (Denmark)

    Ponce-González, Jesús Gustavo; Ara, Ignacio; Larsen, Steen

    2016-01-01

    PURPOSE: The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity. METHOD: Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10...

  14. Regulation and functions of the lms homeobox gene during development of embryonic lateral transverse muscles and direct flight muscles in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dominik Müller

    Full Text Available BACKGROUND: Patterning and differentiation of developing musculatures require elaborate networks of transcriptional regulation. In Drosophila, significant progress has been made into identifying the regulators of muscle development and defining their interactive networks. One major family of transcription factors involved in these processes consists of homeodomain proteins. In flies, several members of this family serve as muscle identity genes to specify the fates of individual muscles, or groups thereof, during embryonic and/or adult muscle development. Herein, we report on the expression and function of a new Drosophila homeobox gene during both embryonic and adult muscle development. METHODOLOGY/PRINCIPAL FINDINGS: The newly described homeobox gene, termed lateral muscles scarcer (lms, which has yet uncharacterized orthologs in other invertebrates and primitive chordates but not in vertebrates, is expressed exclusively in subsets of developing muscle tissues. In embryos, lms is expressed specifically in the four lateral transverse (LT muscles and their founder cells in each hemisegment, whereas in larval wing imaginal discs, it is expressed in myoblasts that develop into direct flight muscles (DFMs, which are important for proper wing positioning. We have analyzed the regulatory inputs of various other muscle identity genes with overlapping or complementary expression patterns towards the cell type specific regulation of lms expression. Further we demonstrate that lms null mutants exhibit reduced numbers of embryonic LT muscles, and null mutant adults feature held-out-wing phenotypes. We provide a detailed description of the pattern and morphology of the direct flight muscles in the wild type and lms mutant flies by using the recently-developed ultramicroscopy and show that, in the mutants, all DFMs are present and present normal morphologies. CONCLUSIONS/SIGNIFICANCE: We have identified the homeobox gene lms as a new muscle identity gene

  15. Skeletal muscle protein synthesis and the abundance of the mRNA translation initiation repressor PDCD4 are inversely regulated by fasting and refeeding in rats.

    Science.gov (United States)

    Zargar, Sana; Moreira, Tracy S; Samimi-Seisan, Helena; Jeganathan, Senthure; Kakade, Dhanshri; Islam, Nushaba; Campbell, Jonathan; Adegoke, Olasunkanmi A J

    2011-06-01

    Optimal skeletal muscle mass is vital to human health, because defects in muscle protein metabolism underlie or exacerbate human diseases. The mammalian target of rapamycin complex 1 is critical in the regulation of mRNA translation and protein synthesis. These functions are mediated in part by the ribosomal protein S6 kinase 1 (S6K1) through mechanisms that are poorly understood. The tumor suppressor programmed cell death 4 (PDCD4) has been identified as a novel substrate of S6K1. Here, we examined 1) the expression of PDCD4 in skeletal muscle and 2) its regulation by feed deprivation (FD) and refeeding. Male rats (~100 g; n = 6) were subjected to FD for 48 h; some rats were refed for 2 h. FD suppressed muscle fractional rates of protein synthesis and Ser(67) phosphorylation of PDCD4 (-50%) but increased PDCD4 abundance (P muscle fractional rates of protein synthesis and reduced PDCD4 abundance relative to FD. Finally, when myoblasts were grown in amino acid- and serum-free medium, phenylalanine incorporation into proteins in cells depleted of PDCD4 more than doubled the values in cells with a normal level of PDCD4 (P skeletal muscle in parallel with the reduction of the abundance of this mRNA translation inhibitor.

  16. Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study.

    Science.gov (United States)

    Kohara, Katsuhiko; Okada, Yoko; Ochi, Masayuki; Ohara, Maya; Nagai, Tokihisa; Tabara, Yasuharu; Igase, Michiya

    2017-08-01

    There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross-sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. Two sarcopenic indices were measured: thigh muscle cross-sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel-type Dementia Assessment Scale, and brachial-ankle pulse wave velocity was measured as an index of arterial stiffness. Both sarcopenic indices were modestly but significantly associated with brachial-ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel-type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  17. Estimation of thigh muscle mass with magnetic resonance imaging in older adults and people with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Mathur, Sunita; Takai, Karen Pr; Macintyre, Donna L; Reid, Darlene

    2008-02-01

    Quantifying muscle mass is an essential part of physical therapy assessment, particularly in older adults and in people with chronic conditions associated with muscle atrophy. The purposes of this study were to examine the relationship between muscle cross-sectional area (CSA) and volume by use of magnetic resonance imaging (MRI) and to compare anthropometric estimations of midthigh CSA with measurements obtained from MRI. Twenty older adults who were healthy and 20 people with chronic obstructive pulmonary disease (COPD), matched for age, sex, and body mass index, underwent MRI to obtain measurements of thigh muscle CSA and volume. Anthropometric measurements (skinfold thickness and thigh circumference) were used to estimate midthigh CSA. Muscle volumes were significantly lower in the people with COPD than in the older adults who were healthy. Moderate to high correlations were found between midthigh CSA and volume in both groups (r=.61-.94). Anthropometric measurements tended to overestimate midthigh CSA in both the people with COPD (estimated CSA=64.9+/-17.8; actual CSA=48.3+/-10.2 cm(2)) and the older adults who were healthy (estimated quadriceps femoris muscle CSA=65.0+/-14.0; actual CSA=56.8+/-13.5 cm(2)). Furthermore, the estimated quadriceps femoris muscle CSAs were not sensitive enough to detect a difference in muscle size between people with COPD and controls. Thigh circumference alone was not different between groups and showed only low to moderate correlations with muscle volume (r=.19-.47). Muscle CSA measured from a single slice provides a good indication of volume, but the most representative slice should be chosen on the basis of the muscle group of interest. Thigh circumference is not correlated with muscle volume and, therefore, should not be used as an indicator of muscle size. The development of population-specific reference equations for estimating muscle CSA from anthropometric measurements is warranted.

  18. Supplementing Breakfast with a Vitamin D and Leucine-Enriched Whey Protein Medical Nutrition Drink Enhances Postprandial Muscle Protein Synthesis and Muscle Mass in Healthy Older Men.

    Science.gov (United States)

    Chanet, Audrey; Verlaan, Sjors; Salles, Jérôme; Giraudet, Christophe; Patrac, Véronique; Pidou, Véronique; Pouyet, Corinne; Hafnaoui, Nordine; Blot, Adeline; Cano, Noël; Farigon, Nicolas; Bongers, Anke; Jourdan, Marion; Luiking, Yvette; Walrand, Stéphane; Boirie, Yves

    2017-12-01

    Background: A promising strategy to help older adults preserve or build muscle mass is to optimize muscle anabolism through providing an adequate amount of high-quality protein at each meal. Objective: This "proof of principle" study investigated the acute effect of supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink on postprandial muscle protein synthesis and longer-term effect on muscle mass in healthy older adults. Methods: A randomized, placebo-controlled, double-blind study was conducted in 24 healthy older men [mean ± SD: age 71 ± 4 y; body mass index (in kg/m 2 ) 24.7 ± 2.8] between September 2012 and October 2013 at the Unit of Human Nutrition, University of Auvergne, Clermont-Ferrand, France. Participants received a medical nutrition drink [test group; 21 g leucine-enriched whey protein, 9 g carbohydrates, 3 g fat, 800 IU cholecalciferol (vitamin D 3 ), and 628 kJ] or a noncaloric placebo (control group) before breakfast for 6 wk. Mixed muscle protein fractional synthesis rate (FSR) was measured at week 0 in the basal and postprandial state, after study product intake with a standardized breakfast with the use of l-[ 2 H 5 ]-phenylalanine tracer methodology. The longer-term effect of the medical nutrition drink was evaluated by measurement of appendicular lean mass, representing skeletal muscle mass at weeks 0 and 6, by dual-energy X-ray absorptiometry. Results: Postprandial FSR (0-240 min) was higher in the test group than in the control group [estimate of difference (ED): 0.022%/h; 95% CI: 0.010%/h, 0.035%/h; ANCOVA, P = 0.001]. The test group gained more appendicular lean mass than the control group after 6 wk (ED: 0.37 kg; 95% CI: 0.03, 0.72 kg; ANCOVA, P = 0.035), predominantly as leg lean mass (ED: 0.30 kg; 95% CI: 0.03, 0.57 kg; ANCOVA, P = 0.034). Conclusions: Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein

  19. Skeletal muscle mass and quality as risk factors for postoperative outcome after open colon resection for cancer

    NARCIS (Netherlands)

    Boer, B. C.; de Graaff, F.; Brusse-Keizer, M.; Bouman, D. E.; Slump, C. H.; Slee-Valentijn, M.; Klaase, J. M.

    The prevalence of colorectal cancer in the elderly is increasing and, therefore, surgical interventions with a risk of potential complications are more frequently performed. This study investigated the role of low skeletal muscle mass (sarcopenia), muscle quality, and the sarcopenic obesity as

  20. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Blauwhoff-Buskermolen, Susanne; Versteeg, Kathelijn S.; de van der Schueren, Marian A. E.; den Braver, Nicole R.; Berkhof, Johannes; Langius, Jacqueline A. E.; Verheul, Henk M. W.

    2016-01-01

    Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall

  1. LOW MID-UPPER ARM CIRCUMFERENCE AND MORTALITY IN OLDER PERSONS: THE INFLUENCE OF FAT AND MUSCLE MASS

    NARCIS (Netherlands)

    Delmonico, M.J.; Harris, T.B.; Visser, M.; Park, S.W.; Conroy, M.B.; Velasquez-Mieyer, P.; Boudreau, R.; Manini, T.M.; Nevitt, M.; Newman, A.B.; Goodpaster, B.H.

    2009-01-01

    Background: Sarcopenia is thought to be accompanied by increased muscle fat infiltration. However, no longitudinal studies have examined concomitant changes in muscle mass, strength, or fat infiltration in older adults. Objective: We present longitudinal data on age-related changes in leg

  2. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Hua Bai

    2013-11-01

    Full Text Available Reduced insulin/IGF signaling increases lifespan in many animals. To understand how insulin/IGF mediates lifespan in Drosophila, we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin/IGF signaling genotypes. Dawdle, an Activin ligand, is bound and repressed by dFOXO when reduced insulin/IGF extends lifespan. Reduced Activin signaling improves performance and protein homeostasis in muscles of aged flies. Activin signaling through the Smad binding element inhibits the transcription of Autophagy-specific gene 8a (Atg8a within muscle, a factor controlling the rate of autophagy. Expression of Atg8a within muscle is sufficient to increase lifespan. These data reveal how insulin signaling can regulate aging through control of Activin signaling that in turn controls autophagy, representing a potentially conserved molecular basis for longevity assurance. While reduced Activin within muscle autonomously retards functional aging of this tissue, these effects in muscle also reduce secretion of insulin-like peptides at a distance from the brain. Reduced insulin secretion from the brain may subsequently reinforce longevity assurance through decreased systemic insulin/IGF signaling.

  3. Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

    Science.gov (United States)

    Rønning, Sissel B; Carlson, Cathrine R; Stang, Espen; Kolset, Svein O; Hollung, Kristin; Pedersen, Mona E

    2015-01-01

    The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

  4. Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

    Directory of Open Access Journals (Sweden)

    Sissel B Rønning

    Full Text Available The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

  5. The effects of dietary protein intake on appendicular lean mass and muscle function in elderly men

    DEFF Research Database (Denmark)

    Mitchell, Cameron J; Milan, Amber M; Mitchell, Sarah M

    2017-01-01

    Background: The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg-1 · d-1 Aging may increase protein requirements, particularly to maintain muscle mass.Objective: We investigated whether controlled protein consumption at the current RDA...... or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.Design: In this parallel-group randomized trial, 29 men aged >70 y [mean ± SD body mass index (in kg/m2): 28.3 ± 4.2] were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg-1 · d-1...... energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P= 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P

  6. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

    Science.gov (United States)

    White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

    2014-11-04

    Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

  7. Dicarbonyl stress and glyoxalase enzyme system regulation in human skeletal muscle.

    Science.gov (United States)

    Mey, Jacob T; Blackburn, Brian K; Miranda, Edwin R; Chaves, Alec B; Briller, Joan; Bonini, Marcelo G; Haus, Jacob M

    2018-02-01

    Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity, and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yr.; BMI: 32 ± 2 kg/m 2 ) compared with lean healthy control subjects (LHC; age: 27 ± 1 yr.; BMI: 22 ± 1 kg/m 2 ). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU·m -2 ·min -1 )-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI, percent body fat, and HOMA-IR, while positively correlating with clamp-derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1, and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

  8. Texture-modified diets are associated with decreased muscle mass in older adults admitted to a rehabilitation ward.

    Science.gov (United States)

    Shimizu, Akio; Maeda, Keisuke; Tanaka, Kei; Ogawa, Mei; Kayashita, Jun

    2018-05-01

    Texture-modified diets (TMD) have significantly lower energy and protein content than normal diets. Therefore, TMD can cause malnutrition and loss of muscle mass. However, few studies have reported the relationship between TMD and decreased skeletal muscle mass. The aim of the present study was to clarify the association between TMD and decreased skeletal muscle mass. We reviewed data of 188 older adult patients who were admitted to a rehabilitation hospital. TMD were defined based on the Japanese Dysphagia Diet Criteria 2013 proposed by the Japanese Society of Dysphagia Rehabilitation. The Mini Nutritional Assessment-Short Form was used to assess nutritional status; dual-energy X-ray absorptiometry was used to measure the skeletal muscle mass index, and the cut-off values for decreased skeletal muscle mass index were based on the Asian Working Group for Sarcopenia; the Functional Independence Measure was used to evaluate activities of daily living. The patients' mean age was 80.6 ± 7.5 years, and 62% were women. A total of 22 patients (11.7%) consumed TMD. A total of 104 patients (55.3%) had decreased skeletal muscle mass, and approximately 90% of them consumed TMD. Decreased skeletal muscle mass index (odds ratio 7.199, 95% confidence interval 1.489-34.805, P ≤ 0.01) and Functional Independence Measure scores (odds ratio 0.972, 95% confidence interval 0.952-0.992, P ≤ 0.01) were independently related to TMD in the multivariate analysis. The TMD group was associated with decreased skeletal muscle mass. Future, prospective studies are necessary to investigate causality. Geriatr Gerontol Int 2018; 18: 698-704. © 2017 Japan Geriatrics Society.

  9. Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization

    DEFF Research Database (Denmark)

    Prats, Clara; Helge, Jørn W; Nordby, Pernille

    2009-01-01

    Glycogen synthase (GS) is considered the rate-limiting enzyme in glycogenesis but still today there is a lack of understanding on its regulation. We have previously shown phosphorylation-dependent GS intracellular redistribution at the start of glycogen re-synthesis in rabbit skeletal muscle (Prats......, C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise......, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated...

  10. Developmental regulation of voltage-sensitive sodium channels in rat skeletal muscle

    International Nuclear Information System (INIS)

    Sherman, S.J.

    1985-01-01

    The developmental regulation of the voltage-sensitive Na + channel in rat skeletal muscle was studied in vivo and in vitro. In triceps surae muscle developing in vivo the development of TTX-sensitive Na + channel occurred primarily during the first three postnatal weeks as determined by the specific binding of [ 3 H]saxitoxin. This development proceeded in two separate phases. The first phase occurs independently of continuing motor neuron innervation and accounts for 60% of the adult density of TTX-sensitive Na + channels. The second phase, which begins about day 11, requires innervation. Muscle cells in primary culture were found to have both TTX-sensitive and insensitive Na + channels. The development of the TTX-sensitive channel, in vitro, paralleled the initial innervation-independent phase of development observed in vivo. The density of TTX-sensitive Na + channels in cultured muscle cells was regulated by electrical activity and cytosolic Ca ++ levels. Pharmacological blockade of the spontaneous electrical activity present in these cells lead to a nearly 2-fold increase in the surface density of TTX-sensitive channels. The turnover time of the TTX-sensitive Na + channel was measured by blocking the incorporation of newly synthesized channels with tunicamycin, an inhibitor of N-linked protein glycosylation. The regulation of channel density by electrical activity, cytosolic Ca ++ levels, and agents affecting cyclic neucleotide levels had no effect on the turnover time of the TTX-sensitive Na + channel, indicating that these regulatory agents instead affect the synthesis of the channel

  11. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

    DEFF Research Database (Denmark)

    Keller, Pernille; Penkowa, Milena; Keller, Charlotte

    2005-01-01

    Contracting muscle fibers produce and release IL-6, and plasma levels of this cytokine are markedly elevated in response to physical exercise. We recently showed autocrine regulation of IL-6 in human skeletal muscle in vivo and hypothesized that this may involve up-regulation of the IL-6 receptor....... Infusion of rhIL-6 to humans had no effect on the mRNA level of the IL-6 receptor, whereas there was an increase at the protein level. IL-6 receptor mRNA increased similarly in muscle of both IL-6 KO mice and wild-type mice in response to exercise. In conclusion, exercise increases IL-6 receptor production....... Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

  12. Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Erica M. [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Niu, MengMeng; Bergholz, Johann [Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China); Jim Xiao, Zhi-Xiong, E-mail: jxiao@bu.edu [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China)

    2015-05-29

    The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification. In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas.

  13. KCl cotransport regulation and protein kinase G in cultured vascular smooth muscle cells.

    Science.gov (United States)

    Adragna, N C; Zhang, J; Di Fulvio, M; Lincoln, T M; Lauf, P K

    2002-05-15

    K-Cl cotransport is activated by vasodilators in erythrocytes and vascular smooth muscle cells and its regulation involves putative kinase/phosphatase cascades. N-ethylmaleimide (NEM) activates the system presumably by inhibiting a protein kinase. Nitrovasodilators relax smooth muscle via cGMP-dependent activation of protein kinase G (PKG), a regulator of membrane channels and transporters. We investigated whether PKG regulates K-Cl cotransport activity or mRNA expression in normal, PKG-deficient-vector-only-transfected (PKG-) and PKG-catalytic-domain-transfected (PKG+) rat aortic smooth muscle cells. K-Cl cotransport was calculated as the Cl-dependent Rb influx, and mRNA was determined by semiquantitative RT-PCR. Baseline K-Cl cotransport was higher in PKG+ than in PKG- cells (p <0.01). At 0.5 mM, NEM stimulated K-Cl cotransport by 5-fold in PKG- but not in PKG+ cells. However, NEM was more potent although less effective to activate K-Cl cotransport in normal (passage 1-3) and PKG+ than in PKG- cells. In PKG- cells, [(dihydroindenyl) oxy] alkanoic acid (300 mM) but not furosemide (1 mM) inhibited K-Cl cotransport. Furthermore, no difference in K-Cl cotransport mRNA expression was observed between these cells. In conclusion, this study shows that manipulation of PKG expression in vascular smooth muscle cells affects K-Cl cotransport activity and its activation by NEM.

  14. Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload.

    Science.gov (United States)

    Washington, Tyrone A; Healey, Julie M; Thompson, Raymond W; Lowe, Larry L; Carson, James A

    2014-09-01

    Aging alters the skeletal muscle response to overload-induced growth. The onset of functional overload is characterized by increased myoblast proliferation and an altered muscle metabolic profile. The onset of functional overload is associated with increased energy demands that are met through the interconversion of lactate and pyruvate via the activity of lactate dehydrogenase (LDH). Testosterone targets many of the processes activated at the onset of functional overload. However, the effect of aging on this metabolic plasticity at the onset of functional overload and how anabolic steroid administration modulates this response is not well understood. The purpose of this study was to determine if aging would alter overload-induced LDH activity and expression at the onset of functional overload and whether anabolic steroid administration would modulate this response. Five-month and 25-month male Fischer 344xF1 BRN were given nandrolone decanoate (ND) or sham injections for 14days and then the plantaris was functionally overloaded (OV) for 3days by synergist ablation. Aging reduced muscle LDH-A & LDH-B activity 70% (pyoung muscle. Our study provides evidence that aging alters aspects of skeletal muscle metabolic plasticity normally induced by overload and anabolic steroid administration. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Effects of adenosine triphosphate concentration on motor force regulation during skeletal muscle contraction

    Science.gov (United States)

    Wei, J.; Dong, C.; Chen, B.

    2017-04-01

    We employ a mechanical model of sarcomere to quantitatively investigate how adenosine triphosphate (ATP) concentration affects motor force regulation during skeletal muscle contraction. Our simulation indicates that there can be negative cross-bridges resisting contraction within the sarcomere and higher ATP concentration would decrease the resistance force from negative cross-bridges by promoting their timely detachment. It is revealed that the motor force is well regulated only when ATP concentration is above a certain level. These predictions may provide insights into the role of ATP in regulating coordination among multiple motors.

  16. Practice and regulations of radiological mass screening in Italy

    International Nuclear Information System (INIS)

    Indovina, P.L.; Romagnoli, S.; Paganini Fioratti, M.

    1987-01-01

    The law setting up the National Health Service in Italy came into force in 1978. This law attributes many public health responsibilities to local government bodies, and these have also power to issue decrees and circulars with regulatory effect. It therefore proved difficult to obtain a complete picture of the regulations in the short time available. However, those laws, decrees and circulars have been traced which impose radiological examinations on individual members of the population as a condition of their carrying out particular activities in work or study. The statistical data on the total number of persons subjected to such examinations each year have been supplied by the Central Institute of Statistics (ISTAT). In some cases it has not been possible to trace any up-to-date statistics. We have understood the term 'mass radiological screening' in a rather wide sense, not as solely mass examination prescribed on the basis of specific regulations. It is for this reason that we have included in the analyses the scoliosis examinations advised by the authorities concerned in only some areas of Italy. For the same reason radiological examination of the dental apparatus has also been taken into consideration, since it is widespread among the population even though there are no regulations on the subject

  17. Lean muscle mass in classic or ovulatory PCOS: association with central obesity and insulin resistance.

    Science.gov (United States)

    Mario, F M; do Amarante, F; Toscani, M K; Spritzer, P M

    2012-10-01

    This age-matched case-control study assessed total and segmental lean muscle mass in classic or ovulatory polycystic ovary syndrome (PCOS) patients and investigated whether lean mass is associated with hormone and metabolic features. Participants underwent anthropometric and clinical evaluation. Habitual physical activity was assessed with a digital pedometer, and body composition by dual-energy X-ray absorptiometry. Laboratory measurements included total cholesterol, cholesterol fractions, triglycerides, glucose, total serum testosterone, serum insulin, estradiol, luteinizing hormone, and SHBG. Energy intake was calculated using a food frequency questionnaire. Classic PCOS patients had higher body mass index (BMI), waist circumference, testosterone and lipid accumulation product values than ovulatory PCOS and controls. Energy consumption, homeostasis model assessment index, SHBG, free androgen index and triglycerides, total and trunk lean mass were higher only in classic PCOS women vs. controls. Arm, leg, trunk, total or limb lean masses were not correlated with hormone levels in any of the groups. However, in PCOS women lipid accumulation product was positively correlated with total (r=0.56, p=0.001), trunk (r=0.59, p=0.001), arm (r=0.54, p=0.001), leg (r=0.44, p=0.03) and limb (r=0.48, p=0.001) lean masses. BMI was positively correlated with all lean mass segments and independently associated with total lean mass. Lipid accumulation product and BMI were independently associated with trunk lean mass variation. The increase in lean mass in classic PCOS appears to be associated with insulin resistance and central obesity rather than with energy intake, physical activity or androgens. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  18. Initial Presentation of Renal Cell Carcinoma as a Metastatic Mass within the Masseter Muscle: A Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyung Eun; Lee, Han Bee; Cho, Woo Ho; Kim, Jae Hyung; Lee, Ji Hae; Kang, Min Jin [Dept. of Radiology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kim, Hyun Jung [Dept. of Pathology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

    2012-02-15

    Renal cell carcinoma (RCC) is often concomitant with distant metastasis, and these metastases are the first sign of an otherwise occult primary. Whereas metastasis of RCC to the head and neck has been reported, metastasis to the masseter muscle, which is composed of skeletal muscle, is quite rare. We now report the case of a 66-year-old man who had a past history of pulmonary tuberculosis, with RCC metastasis of a well-defined intensely enhancing hypervascular mass in the masseter muscle as the initial presentation. We present the imaging findings of this case and a literature review about radiologic differential diagnosis of intramasseteric masses.

  19. Type VI collagen turnover-related peptides—novel serological biomarkers of muscle mass and anabolic response to loading in young men

    DEFF Research Database (Denmark)

    Nedergaard, Anders; Sun, Shu; Karsdal, Morten A

    2013-01-01

    Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflec...

  20. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  1. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Osada, Takuya; Andersen, Lisbeth Tingsted

    2005-01-01

    before exercise and 2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near resting levels within 5 hours in the HC trial, but remained depressed through 24 hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose uptake was 5- to 15-fold higher with HC ingestion......In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9...... male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% V¿o2max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and tissue frozen from vastus lateralis muscle biopsies obtained...

  2. Regulation of angiogenesis in human skeletal muscle with specific focus on pro- angiogenic and angiostatic factors

    DEFF Research Database (Denmark)

    Høier, Birgitte

    It is well established that acute exercise promotes an angiogenic response and that a period of exercise training results in capillary growth. Skeletal muscle angiogenesis is a complex process that requires a coordinated interplay of multiple factors and compounds to ensure proper vascular function....... The angiogenic process is initiated through changes in mechanical and/or metabolic factors during exercise and when exercise is repeated these stimuli may result in capillary growth if needed. The present PhD thesis is based on six studies in which the regulation of angiogenesis in skeletal muscle...... was studied in peripheral arterial disease. Vascular endothelial growth factor (VEGF) is the most important factor in exercise-induced angiogenesis and is located primarily in muscle cells but also in endothelial cells, pericytes, and in the extracellular matrix. VEGF protein secretion to the interstitium...

  3. The role of fat mass and skeletal muscle mass in knee osteoarthritis is different for men and women: the NEO study

    NARCIS (Netherlands)

    Visser, A.W. de; Mutsert, R. de; Loef, M.; Cessie, S. le; Heijer, M. den; Bloem, J.L.; Reijnierse, M.; Rosendaal, F.R.; Kloppenburg, M.; Assendelft, W.J.J.; Smit, J.W.A.; et al.,

    2014-01-01

    OBJECTIVE: To investigate if the amount of fat mass (FM) or skeletal muscle mass (SMM) is more strongly associated with knee osteoarthritis (OA), in both men and women. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45-65 years, including 5313

  4. Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling.

    Science.gov (United States)

    Miller, Eileen; Czopek, Alicja; Duthie, Karolina M; Kirkby, Nicholas S; van de Putte, Elisabeth E Fransen; Christen, Sibylle; Kimmitt, Robert A; Moorhouse, Rebecca; Castellan, Raphael F P; Kotelevtsev, Yuri V; Kuc, Rhoda E; Davenport, Anthony P; Dhaun, Neeraj; Webb, David J; Hadoke, Patrick W F

    2017-02-01

    The role of smooth muscle endothelin B (ET B ) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ET B receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ET B receptors were selectively deleted from smooth muscle by crossing floxed ET B mice with those expressing cre-recombinase controlled by the transgelin promoter. Functional consequences of ET B deletion were assessed using myography. BP was measured by telemetry, and neointimal lesion formation induced by femoral artery injury. Lesion size and composition (day 28) were analyzed using optical projection tomography, histology, and immunohistochemistry. Selective deletion of ET B was confirmed by genotyping, autoradiography, polymerase chain reaction, and immunohistochemistry. ET B -mediated contraction was reduced in trachea, but abolished from mesenteric veins, of knockout mice. Induction of ET B -mediated contraction in mesenteric arteries was also abolished in these mice. Femoral artery function was unaltered, and baseline BP modestly elevated in smooth muscle ET B knockout compared with controls (+4.2±0.2 mm Hg; P<0.0001), but salt-induced and ET B blockade-mediated hypertension were unaltered. Circulating endothelin-1 was not altered in knockout mice. ET B -mediated contraction was not induced in femoral arteries by incubation in culture medium or lesion formation, and lesion size was not altered in smooth muscle ET B knockout mice. In the absence of other pathology, ET B receptors in vascular smooth muscle make a small but significant contribution to ET B -dependent regulation of BP. These ET B receptors have no effect on vascular contraction or neointimal remodeling. © 2016 The Authors.

  5. Memories of early work on muscle contraction and regulation in the 1950's and 1960's

    International Nuclear Information System (INIS)

    Huxley, Hugh E.

    2008-01-01

    Professor Ebashi's epic work on the biochemistry of the regulation of muscle contraction began in the early 1950's, during the same period that work on the molecular basis of force production in muscle was also beginning. The latter work started in two MRC Research Units in the UK, and was continued jointly by the two workers from those Units who had, independently, gone to MIT to learn the new techniques of electron microscopy and to apply them to muscle. In a somewhat similar fashion, Professor Ebashi also spent one or two years in the USA, continuing his work on the role of calcium in muscle regulation in Lippman's laboratory, before returning to Japan to achieve the great breakthroughs in this work during the 1960's. Hanson and Huxley, after putting forward the overlapping actin and myosin filament arrays model for the striated muscle sarcomere, and subsequently the sliding filament model of muscle contraction (simultaneously with A.F Huxley and R. Niedergerke), returned to the UK to pursue detailed structural studies in separate Research Units, in a mixture of consultation, collaboration, and competition, during the later 1950's and throughout the 1960's. However, the path to enlightenment described here in some detail was somewhat more tortuous than the standard literature perhaps reveals. Nevertheless, by the time of the Cold Spring Harbor Symposium on Muscle Contraction in 1972, the two lines of enquiry on regulation itself, and on the tilting cross-bridge model of force production, had arrived at a good deal of common ground, and indeed the identification of troponin and its periodic distribution along the actin filaments had helped resolve a long-standing puzzle in the interpretation of the low angle X-ray diagram. Since then, an enormous amount of remarkable new work has been necessary to establish troponin regulation and the tilting cross-bridge mechanism in molecular detail, but the work in the 1950's and 1960's has provided a firm and accurate basis

  6. Relative muscle mass and the risk of incident type 2 diabetes: A cohort study.

    Directory of Open Access Journals (Sweden)

    Sungwoo Hong

    Full Text Available The association between relative muscle mass (RMM and incidence of type 2 diabetes (T2DM is largely unknown. We examined whether RMM predicted development of T2DM in an apparently young healthy population.This cohort study was comprised of 113,913 men and 89,854 women, free of T2DM at baseline, who underwent a health checkup examination and were followed-up annually or biennially for an average of 2.9 years. We used skeletal muscle mass index (SMI as an indicator of RMM. SMI (% [total skeletal muscle mass (kg/body weight (kg×100] was estimated using a bioelectrical impedance analyzer. The study outcome was incident T2DM, defined as fasting serum glucose ≥126 mg/dL, HbA1C ≥6.5%, or use of medication for T2DM.During 589,098.8 person-years of follow-up, 4,264 individuals developed T2DM (incidence rate, 7.2 per 1000 person-years. Median age (range at baseline was 39.1 years (18.1-87.1. RMM was negatively associated with incidence of T2DM in a dose-response manner. The multivariate-adjusted hazard ratios (95% CIs for incident T2DM comparing quartiles 3, 2 and 1 of RMM to the highest quartile were 1.32 (1.14-1.52, 1.63 (1.42-1.86, and 2.21 (1.94-2.51, respectively, for males and 1.18 (0.88-1.58, 1.46 (1.11-1.91, and 1.96 (01.51-2.53 for females (P for trend <0.001; 0.011. This association was stronger in younger or premenopausal subjects.RMM was negatively associated with development of T2DM in a large sample of young and middle-aged Korean adults. Further research is required to determine whether preservation of muscle mass through intervention affects the risk of T2DM.

  7. Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79 : the health, aging and body composition study

    NARCIS (Netherlands)

    Visser, Marjolein; Kritchevsky, Stephen B; Goodpaster, Bret H; Newman, Anne B; Nevitt, Michael; Stamm, Elizabeth; Harris, Tamara B

    OBJECTIVES: The loss of muscle mass with aging, or sarcopenia, is hypothesized to be associated with the deterioration of physical function. Our aim was to determine whether low leg muscle mass and greater fat infiltration in the muscle were associated with poor lower extremity performance (LEP).

  8. The effect of individualized nutritional counseling on muscle mass and treatment outcome in patients with metastatic colorectal cancer undergoing chemotherapy: a randomized controlled trial protocol

    NARCIS (Netherlands)

    van der Werf, Anne; Blauwhoff-Buskermolen, Susanne; Langius, Jacqueline A. E.; Berkhof, Johannes; Verheul, Henk M. W.; de van der Schueren, Marian A. E.

    2015-01-01

    A low muscle mass is prevalent in patients with metastatic colorectal cancer (mCRC) and has been associated with poor treatment outcome. Chemotherapeutic treatment has an additional unfavorable effect on muscle mass. Sufficient protein intake and physical activity are known to induce muscle protein

  9. Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle.

    Science.gov (United States)

    Vichaiwong, Kanokwan; Purohit, Suneet; An, Ding; Toyoda, Taro; Jessen, Niels; Hirshman, Michael F; Goodyear, Laurie J

    2010-10-15

    TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab-GAP (GTPase-activating protein) that is highly expressed in skeletal muscle, but little is known about TBC1D1 regulation and function. We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites (Ser231, Ser660 and Ser700) and one predicted Akt phosphorylation site (Thr590) in control mice, AMPKα2 inactive transgenic mice (AMPKα2i TG) and Akt2-knockout mice (Akt2 KO). Muscle contraction significantly increased TBC1D1 phosphorylation on Ser231 and Ser660, tended to increase Ser700 phosphorylation, but had no effect on Thr590. AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside) also increased phosphorylation on Ser231, Ser660 and Ser700, but not Thr590, whereas insulin only increased Thr590 phosphorylation. Basal and contraction-stimulated TBC1D1 Ser231, Ser660 and Ser700 phosphorylation were greatly reduced in AMPKα2i TG mice, although contraction still elicited a small increase in phosphorylation. Akt2 KO mice had blunted insulin-stimulated TBC1D1 Thr590 phosphorylation. Contraction-stimulated TBC1D1 Ser231 and Ser660 phosphorylation were normal in high-fat-fed mice. Glucose uptake in vivo was significantly decreased in tibialis anterior muscles overexpressing TBC1D1 mutated on four predicted AMPK phosphorylation sites. In conclusion, contraction causes site-specific phosphorylation of TBC1D1 in skeletal muscle, and TBC1D1 phosphorylation on AMPK sites regulates contraction-stimulated glucose uptake. AMPK and Akt regulate TBC1D1 phosphorylation, but there must be additional upstream kinases that mediate TBC1D1 phosphorylation in skeletal muscle.

  10. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    Energy Technology Data Exchange (ETDEWEB)

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  11. Role for tryptophan in regulation of protein synthesis in porcine muscle

    International Nuclear Information System (INIS)

    Lin, F.D.; Smith, T.K.; Bayley, H.S.

    1988-01-01

    Experiments were conducted to determine the effect of varying concentrations of dietary tryptophan on growth rate and protein synthesis in edible muscle tissues of growing swine. A total of 45 immature swine (initial weight approximately 24 kg) were fed corn-gelatin diets containing 0.5 (n = 8), 0.8 (n = 10), 1.3 (n = 10), 1.5 (n = 7) or 2.0 (n = 10) g tryptophan/kg diet for 35 d. Animals fed 0.5 and 0.8 g tryptophan/kg grew more slowly, consumed less feed and had a lower efficiency of feed utilization than animals fed higher concentrations of tryptophan. Thirty similar animals were used in a second experiment. Diets containing 0.5, 0.8, 1.0, 1.5 or 2.0 g tryptophan/kg diet (n = 6) were fed for 14 d, after which all animals were killed and samples were taken of longissimus dorsi, triceps brachii and biceps femoris. Protein synthetic activity was determined by monitoring the incorporation of [ 14 C]phenylalanine into protein in vitro. There was no significant difference in synthetic activity between different muscle types. There was no effect of diet on the activity of the muscle soluble protein fraction. The activity of the muscle ribosomal fraction, however, was positively correlated with increasing concentrations of dietary tryptophan. It was concluded that tryptophan has the potential to regulate muscle protein synthesis in a manner beyond serving simply as a component of protein

  12. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    International Nuclear Information System (INIS)

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-01-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH 4 Cl x 100 g body wt -1 x day -1 . Epitrochlearis muscles were incubated with L-[1- 14 C]-valine and L-[1- 14 C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain α-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain α-keto acid dehydrogenase

  13. Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle

    Science.gov (United States)

    Ali, Mehboob

    2015-01-01

    Preliminary proteomics studies between tonic vs. phasic smooth muscles identified three distinct protein spots identified to be those of transgelin (SM22). The latter was found to be distinctly downregulated in the internal anal sphincter (IAS) vs. rectal smooth muscle (RSM) SMC. The major focus of the present studies was to examine the differential molecular control mechanisms by SM22 in the functionality of truly tonic smooth muscle of the IAS vs. the adjoining phasic smooth muscle of the RSM. We monitored SMC lengths before and after incubation with pFLAG-SM22 (for SM22 overexpression), and SM22 small-interfering RNA. pFLAG-SM22 caused concentration-dependent and significantly greater relaxation in the IAS vs. the RSM SMCs. Conversely, temporary silencing of SM22 caused contraction in both types of the SMCs. Further studies revealed a significant reverse relationship between the levels of SM22 phosphorylation and the amount of SM22-actin binding in the IAS and RSM SMC. Data showed higher phospho-SM22 levels and decreased SM22-actin binding in the IAS, and reverse to be the case in the RSM SMCs. Experiments determining the mechanism for SM22 phosphorylation in these smooth muscles revealed that Y-27632 (Rho kinase inhibitor) but not Gö-6850 (protein kinase C inhibitor) caused concentration-dependent decreased phosphorylation of SM22. We speculate that SM22 plays an important role in the regulation of basal tone via Rho kinase-induced phosphorylation of SM22. PMID:25617350

  14. Chaperones and the Proteasome System: Regulating the Construction and Demolition of Striated Muscle

    Directory of Open Access Journals (Sweden)

    Casey Carlisle

    2017-12-01

    Full Text Available Protein folding factors (chaperones are required for many diverse cellular functions. In striated muscle, chaperones are required for contractile protein function, as well as the larger scale assembly of the basic unit of muscle, the sarcomere. The sarcomere is complex and composed of hundreds of proteins and the number of proteins and processes recognized to be regulated by chaperones has increased dramatically over the past decade. Research in the past ten years has begun to discover and characterize the chaperones involved in the assembly of the sarcomere at a rapid rate. Because of the dynamic nature of muscle, wear and tear damage is inevitable. Several systems, including chaperones and the ubiquitin proteasome system (UPS, have evolved to regulate protein turnover. Much of our knowledge of muscle development focuses on the formation of the sarcomere but recent work has begun to elucidate the requirement and role of chaperones and the UPS in sarcomere maintenance and disease. This review will cover the roles of chaperones in sarcomere assembly, the importance of chaperone homeostasis and the cooperation of chaperones and the UPS in sarcomere integrity and disease.

  15. ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation

    Directory of Open Access Journals (Sweden)

    Timothy J. Mead

    2018-04-01

    Full Text Available Summary: Focal adhesions anchor cells to extracellular matrix (ECM and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

  16. Concurrent Label-Free Mass Spectrometric Analysis of Dystrophin Isoform Dp427 and the Myofibrosis Marker Collagen in Crude Extracts from mdx-4cv Skeletal Muscles

    Science.gov (United States)

    Murphy, Sandra; Zweyer, Margit; Mundegar, Rustam R.; Henry, Michael; Meleady, Paula; Swandulla, Dieter; Ohlendieck, Kay

    2015-01-01

    The full-length dystrophin protein isoform of 427 kDa (Dp427), the absence of which represents the principal abnormality in X-linked muscular dystrophy, is difficult to identify and characterize by routine proteomic screening approaches of crude tissue extracts. This is probably related to its large molecular size, its close association with the sarcolemmal membrane, and its existence within a heterogeneous glycoprotein complex. Here, we used a careful extraction procedure to isolate the total protein repertoire from normal versus dystrophic mdx-4cv skeletal muscles, in conjunction with label-free mass spectrometry, and successfully identified Dp427 by proteomic means. In contrast to a considerable number of previous comparative studies of the total skeletal muscle proteome, using whole tissue proteomics we show here for the first time that the reduced expression of this membrane cytoskeletal protein is the most significant alteration in dystrophinopathy. This agrees with the pathobiochemical concept that the almost complete absence of dystrophin is the main defect in Duchenne muscular dystrophy and that the mdx-4cv mouse model of dystrophinopathy exhibits only very few revertant fibers. Significant increases in collagens and associated fibrotic marker proteins, such as fibronectin, biglycan, asporin, decorin, prolargin, mimecan, and lumican were identified in dystrophin-deficient muscles. The up-regulation of collagen in mdx-4cv muscles was confirmed by immunofluorescence microscopy and immunoblotting. Thus, this is the first mass spectrometric study of crude tissue extracts that puts the proteomic identification of dystrophin in its proper pathophysiological context. PMID:28248273

  17. Baseline muscle mass is a poor predictor of functional overload-induced gain in the mouse model

    Directory of Open Access Journals (Sweden)

    Audrius Kilikevicius

    2016-11-01

    Full Text Available Genetic background contributes substantially to individual variability in muscle mass. Muscle hypertrophy in response to resistance training can also vary extensively. However, it is less clear if muscle mass at baseline is predictive of the hypertrophic response.The aim of this study was to examine the effect of genetic background on variability in muscle mass at baseline and in the adaptive response of the mouse fast- and slow-twitch muscles to overload. Males of eight laboratory mouse strains: C57BL/6J (B6, n=17, BALB/cByJ (n=7, DBA/2J (D2, n=12, B6.A-(rs3676616-D10Utsw1/Kjn (B6.A, n=9, C57BL/6J-Chr10A/J/NaJ (B6.A10, n=8, BEH+/+ (n=11, BEH (n=12 and DUHi (n=12, were studied. Compensatory growth of soleus and plantaris muscles was triggered by a 4-week overload induced by synergist unilateral ablation. Muscle weight in the control leg (baseline varied from 5.2±07 mg soleus and 11.4±1.3 mg plantaris in D2 mice to 18.0±1.7 mg soleus in DUHi and 43.7±2.6 mg plantaris in BEH (p<0.001 for both muscles. In addition, soleus in the B6.A10 strain was ~40% larger (p<0.001 compared to the B6. Functional overload increased muscle weight, however, the extent of gain was strain-dependent for both soleus (p<0.01 and plantaris (p<0.02 even after accounting for the baseline differences. For the soleus muscle, the BEH strain emerged as the least responsive, with a 1.3-fold increase, compared to a 1.7-fold gain in the most responsive D2 strain, and there was no difference in the gain between the B6.A10 and B6 strains. The BEH strain appeared the least responsive in the gain of plantaris as well, 1.3-fold, compared to ~1.5-fold gain in the remaining strains. We conclude that variation in muscle mass at baseline is not a reliable predictor of that in the overload-induced gain. This suggests that a different set of genes influence variability in muscle mass acquired in the process of normal development, growth and maintenance, and in the process of adaptive

  18. Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Veronica; Saraff, Kumuda [Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262 (United States); Medh, Jheem D., E-mail: jheem.medh@csun.edu [Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262 (United States)

    2009-11-06

    Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.

  19. Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression

    Directory of Open Access Journals (Sweden)

    Giuliana Rossi

    2016-03-01

    Full Text Available Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway.

  20. AMP-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient?

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Wojtaszewski, Jørgen; Richter, Erik

    2009-01-01

    In skeletal muscle, the contraction-activated heterotrimeric 5'-AMP-activated protein kinase (AMPK) protein is proposed to regulate the balance between anabolic and catabolic processes by increasing substrate uptake and turnover in addition to regulating the transcription of proteins involved...... in mitochondrial biogenesis and other aspects of promoting an oxidative muscle phenotype. Here, the current knowledge on the expression of AMPK subunits in human quadriceps muscle and evidence from rodent studies suggesting distinct AMPK subunit expression pattern in different muscle types is reviewed. Then......, the intensity and time dependence of AMPK activation in human quadriceps and rodent muscle are evaluated. Subsequently, a major part of this review critically examines the evidence supporting a necessary and/or sufficient role of AMPK in a broad spectrum of skeletal muscle contraction-relevant processes...

  1. Per meal dose and frequency of protein consumption is associated with lean mass and muscle performance.

    Science.gov (United States)

    Loenneke, Jeremy P; Loprinzi, Paul D; Murphy, Caoileann H; Phillips, Stuart M

    2016-12-01

    It has been hypothesized that for older adults evenly distributing consumption of protein at 30-40 g per meal throughout the day may result in more favorable retention of lean mass and muscular strength. Such a thesis has not, to our knowledge, been tested outside of short-term studies or acute measures of muscle protein synthesis. To examine whether the number of times an individual consumed a minimum of 30 g of protein at a meal is associated with leg lean mass and knee extensor strength. Data from the 1999-2002 NHANES were used, with 1081 adults (50-85 y) constituting the analytic sample. A "multiple pass" 24-h dietary interview format was used to collect detailed information about the participants' dietary intake. Knee extensor strength was assessed objectively using the Kin Com MP dynamometer. Leg lean mass was estimated from whole-body dual-energy X-ray absorptiometry (DXA) scans. Participants with 1 vs. 0 (β adjusted  = 23.6, p = 0.002) and 2 vs. 0 (β adjusted  = 51.1, p = 0.001) meals of ≥30 g protein/meal had greater strength and leg lean mass (1 vs. 0, β adjusted  = 1160, p frequency with leg lean mass and strength plateaued at ∼45 g protein/meal for those consuming 2 vs. 0 meals above the evaluated protein/meal threshold. However, for those with only 1 meal at or above the evaluated threshold, the response plateaued at 30 g/meal. Leg lean mass mediated the relationship between protein frequency and strength, with the proportion of the total effect mediated being 64%. We found that more frequent consumption of meals containing between 30 and 45 g protein/meal produced the greatest association with leg lean mass and strength. Thus, the consumption of 1-2 daily meals with protein content from 30 to 45 g may be an important strategy for increasing and/or maintaining lean body mass and muscle strength with aging. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth muscle cell migration

    OpenAIRE

    Venkatesan, Balachandar; Valente, Anthony J.; Reddy, Venkatapuram Seenu; Siwik, Deborah A.; Chandrasekar, Bysani

    2009-01-01

    Vascular smooth muscle cell (SMC) migration is an important mechanism in atherogenesis and postangioplasty arterial remodeling. Previously, we demonstrated that the proinflammatory cytokine interleukin (IL)-18 is a potent inducer of SMC migration. Since extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates ECM degradation and facilitates cell migration, we investigated whether IL-18 and EMMPRIN regulate each other's expression, whether their cross talk induces SMC migration, and...

  3. Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration

    Directory of Open Access Journals (Sweden)

    Juan Mendizabal-Zubiaga

    2016-10-01

    Full Text Available The cannabinoid type 1 (CB1 receptor is widely distributed in the brain and peripheral organs where it regulates cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB1, where it regulates cellular respiration and energy production. Likewise, CB1 is localized on muscle mitochondria, but very little is known about it. The aim of this study was to further investigate in detail the distribution and functional role of mtCB1 in three different striated muscles. Immunoelectron microscopy for CB1 was used in skeletal muscles (gastrocnemius and rectus abdominis and myocardium from wild-type and CB1-KO mice. Functional assessments were performed in mitochondria purified from the heart of the mice and the mitochondrial oxygen consumption upon application of different acute delta-9-tetrahidrocannabinol (Δ9-THC concentrations (100 nM or 200 nM was monitored. About 26% of the mitochondrial profiles in gastrocnemius, 22% in the rectus abdominis and 17% in the myocardium expressed CB1. Furthermore, the proportion of mtCB1 versus total CB1 immunoparticles was about 60% in the gastrocnemius, 55% in the rectus abdominis and 78% in the myocardium. Importantly, the CB1 immunolabeling pattern disappeared in muscles of CB1-KO mice. Functionally, acute 100 nM or 200 nM THC treatment specifically decreased mitochondria coupled respiration between 12% and 15% in wild-type isolated mitochondria of myocardial muscles but no significant difference was noticed between THC treated and vehicle in mitochondria isolated from CB1-KO heart. Furthermore, gene expression of key enzymes involved in pyruvate synthesis, tricarboxylic acid (TCA cycle and mitochondrial respiratory chain was evaluated in the striated muscle of CB1-WT and CB1-KO. CB1-KO showed an increase in the gene expression of Eno3, Pkm2, and Pdha1, suggesting an increased production of pyruvate. In contrast, no significant

  4. Resistance Exercise Impacts Lean Muscle Mass in Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Kogure, Gislaine Satyko; Miranda-Furtado, Cristiana Libardi; Silva, Rafael Costa; Melo, Anderson Sanches; Ferriani, Rui Alberto; De Sá, Marcos Felipe Silva; Dos Reis, Rosana Maria

    2016-04-01

    This study investigated the effects of progressive resistance training (PRT) on lean muscle mass (LMM) in women with or without polycystic ovary syndrome (PCOS) and its effects on metabolic factors and concentrations of related steroid hormones. This was a nonrandomized, therapeutic, open, single-arm study. All in all, 45 sedentary women with PCOS and 52 without (non-PCOS), 18-37 yr of age, with body mass indexes (BMI) of 18-39.9 kg·m(-2) of all races and social status, performed PRT three times a week for 4 months. Before and after PRT, the concentrations of hormones and metabolic factors and waist circumference were measured. LMM and total body fat percentage were determined using dual-energy x-ray absorptiometry. Clinical characteristics, LMM, and fasting glucose were adjusted for confounding covariables and compared using general linear mixed models. Each patient's menstrual history was taken before study enrollment and after PRT. PRT resulted in reduced plasma testosterone and fasting glucose levels. After PRT, the androstenedione concentration increased and the sex hormone-binding globulin concentration decreased in women with PCOS. The waist circumference was reduced (P lean mass (LM)/height2, increased in women with PCOS (P = 0.04). Women with PCOS showed increased muscle mass indexes of appendicular LM/height2 (P = 0.03) and LM/height2 (P women with PCOS (P = 0.01) at the baseline and after PRT. To our knowledge, this is the first report to show that resistance exercise alone can improve hyperandrogenism, reproductive function, and body composition by decreasing visceral fat and increasing LMM, but it has no metabolic impact on women with PCOS.

  5. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

    DEFF Research Database (Denmark)

    Klefter, O.; Feldt-Rasmussen, U.

    2009-01-01

    to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...... in muscle mass occurred during the first 12 months of therapy. Most trials measuring BMD/BMC reported significant increases from baseline values. The significant increases in BMD/BMC occurred after 12-18 months of treatment, i.e. usually later than the increases in muscle parameters. Only seven trials...

  6. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

    DEFF Research Database (Denmark)

    Klefter, Oliver; Feldt-Rasmussen, Ulla

    2009-01-01

    to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...... in muscle mass occurred during the first 12 months of therapy. Most trials measuring BMD/BMC reported significant increases from baseline values. The significant increases in BMD/BMC occurred after 12-18 months of treatment, i.e. usually later than the increases in muscle parameters. Only seven trials...

  7. A dietary supplementation with leucine and antioxidants is capable to accelerate muscle mass recovery after immobilization in adult rats.

    Directory of Open Access Journals (Sweden)

    Isabelle Savary-Auzeloux

    Full Text Available Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6-8 months were subjected to unilateral hindlimb casting for 8 days (I0-I8 and then permitted to recover for 10 to 40 days (R10-R40. They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX (I0 to I8, AOX and leucine (AOX + LEU (I8 to R15 and LEU alone (R15 to R40. Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP and post absorptive (PA states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37% in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40 due to a higher protein synthesis both in PA and PP states (+23% and 31% respectively, Experimental vs. Control diets, P<0.05, R40 without difference in trypsin- and chymotrypsin-like activities between diets. Thus, this nutritional supplementation accelerated the recovery of muscle mass via a stimulation of protein synthesis throughout the entire day (in the PP and PA states and could be a promising strategy to be tested during recovery from bed rest in humans.

  8. Relationship between lifting performance and skeletal muscle mass in elite powerlifters.

    Science.gov (United States)

    Ye, X; Loenneke, J P; Fahs, C A; Rossow, L M; Thiebaud, R S; Kim, D; Bemben, M G; Abe, T

    2013-08-01

    Aim of the study was to examine the relationship between whole body skeletal muscle mass (SMM) and powerlifting performance in elite powerlifters. Twenty elite male powerlifters, including 4 world champions, volunteered. Muscle thickness (MTH) and subcutaneous fat thickness (FTH) were measured by ultrasound at 9 sites on the anterior and posterior aspects of the body. FTH was used to estimate body fat and fat-free mass and SMM was estimated from ultrasound-derived prediction equations. Best lifting performance in the squat (SQ), bench press (BP), and dead lift (DL) was recorded from competition performance. Significant strong correlations (Pwide range of weight classes (56kg-145kg) and there were no significant correlation between the SMM and those performances (r=0.21 for SQ and r=0.12 for BP). However, the DL/SMM ratio was negatively correlated to DL performance (r=-0.47, P<0.05). SMM is a good predictor of powerlifting performance throughout all weight classes.

  9. Regulation of collagen biosynthesis in cultured bovine aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Stepp, M.A.

    1986-01-01

    Aortic smooth muscles cells have been implicated in the etiology of lesions which occur in atherosclerosis and hypertension. Both diseases involve proliferation of smooth muscle cells and accumulation of excessive amounts of extracellular matrix proteins, including collagen type I and type III produced by the smooth muscle cells. To better understand the sites of regulation of collagen biosynthesis and to correlate these with the growth rate of the cells, cultured bovine aortic smooth muscle cells were studied as a function of the number of days (3 to 14) in second passage. Cells grew rapidly up to day 6 when confluence was reached. The total incorporation of [ 3 H]-proline into proteins was highest at day 3 and decreased to a constant level after the cultures reached confluence. In contrast, collagen protein production was lowest before confluence and continued to increase over the entire time course of the experiments. cDNA clones for the α1 and α2 chains of type I and the α1 chain of type III collagen were used to quantitate the steady state level of collagen mRNAs. RNA was tested in a cell-free translation system. Changes in the translational activity of collagen mRNAs parallelled the observed increases in collagen protein production. Thus, at later time points, collagen mRNAs are more active in directing synthesis of preprocollagens, even though less collagen mRNA is present. The conclusion is that the site of regulation of the expression of collagen genes is a function of the growth rate of cultured smooth muscle cells

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

    Science.gov (United States)

    Gordon, Bradley S; Steiner, Jennifer L; Rossetti, Michael L; Qiao, Shuxi; Ellisen, Leif W; Govindarajan, Subramaniam S; Eroshkin, Alexey M; Williamson, David L; Coen, Paul M

    2017-12-01

    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. Copyright © 2017 the American Physiological Society.

  11. Low appendicular skeletal muscle mass (ASM) with limited mobility and poor health outcomes in middle-aged African Americans.

    Science.gov (United States)

    Malmstrom, Theodore K; Miller, Douglas K; Herning, Margaret M; Morley, John E

    2013-09-01

    Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical syndrome associated with the loss of both skeletal muscle mass and muscle function that occurs with aging. Validation of sarcopenia definitions that include both low muscle mass and poor muscle function is needed. In the population-based African American Health (AAH) study (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4 (2004). Muscle mass was measured using dual energy x-ray absorptiometry and mobility by a 6-min walk test and 4-m gait walk test. Height corrected appendicular skeletal mass (ASM; 9.0 ± 1.5 in n = 124 males, 8.3 ± 2.2 in n = 195 females) was computed as total lean muscle mass in arms and legs (kilograms) divided by the square of height (meters). Cross-sectional and longitudinal (6-year) associations of low ASM (bottom 25 % AAH sample; ASM with limited mobility (4-m gait walk ≤1 m/s or 6-min walk ASM with limited mobility was associated with IADL difficulties (p = .008) and frailty (p = .040) but not with ADL difficulties or falls in cross-sectional analyses; and with ADL difficulties (p = .022), IADL difficulties (p = .006), frailty (p = .039), and mortality (p = .003) but not with falls in longitudinal analyses adjusted for age and gender. Low ASM alone was marginally associated with mortality (p = .085) but not with other outcomes in cross-sectional or longitudinal analyses. Low ASM with limited mobility is associated with poor health outcomes among late middle-aged African Americans.

  12. Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1.

    Science.gov (United States)

    Tarnopolsky, Mark; Mahoney, Douglas; Thompson, Terry; Naylor, Heather; Doherty, Timothy J

    2004-01-01

    Creatine monohydrate (CrM) supplementation may increase strength in some types of muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1) did not find a significant treatment effect, but measurements of muscle phosphocreatine (PCr) were not performed. We completed a randomized, double-blind, cross-over trial using 34 genetically confirmed adult DM1 patients without significant cognitive impairment. Participants received CrM (5 g, approximately 0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out. Spirometry, manual muscle testing, quantitative isometric strength testing of handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion endurance, functional tasks, activity of daily living scales, body composition (total, bone, and fat-free mass), serum creatine kinase activity, serum creatinine concentration and clearance, and liver function tests were completed before and after each intervention, and muscle PCr/beta-adenosine triphosphate (ATP) ratios of the forearm flexor muscles were completed at the end of each phase. CrM supplementation did not increase any of the outcome measurements except for plasma creatinine concentration (but not creatinine clearance). Thus, CrM supplementation at 5 g daily does not have any effects on muscle strength, body composition, or activities of daily living in patients with DM1, perhaps because of a failure of the supplementation to increase muscle PCr/beta-ATP content.

  13. Relation between body mass index percentile and muscle strength and endurance

    Directory of Open Access Journals (Sweden)

    Noha Abdel Kader Abdel Kader Hasan

    2016-10-01

    Conclusion: The study shows that the BMI of children had a positive correlation with the muscle strength of quadriceps, triceps, and abdominal muscles while a negative correlation with the endurance time of these muscles.

  14. Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease.

    Science.gov (United States)

    Mittal, Ravinder K

    2016-09-01

    Muscularis propria throughout the entire gastrointestinal tract including the esophagus is comprised of circular and longitudinal muscle layers. Based on the studies conducted in the colon and the small intestine, for more than a century, it has been debated whether the two muscle layers contract synchronously or reciprocally during the ascending contraction and descending relaxation of the peristaltic reflex. Recent studies in the esophagus and colon prove that the two muscle layers indeed contract and relax together in almost perfect synchrony during ascending contraction and descending relaxation of the peristaltic reflex, respectively. Studies in patients with various types of esophageal motor disorders reveal temporal disassociation between the circular and longitudinal muscle layers. We suggest that the discoordination between the two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain. Certain pathologies may selectively target one and not the other muscle layer, e.g., in eosinophilic esophagitis there is a selective dysfunction of the longitudinal muscle layer. In achalasia esophagus, swallows are accompanied by the strong contraction of the longitudinal muscle without circular muscle contraction. The possibility that the discoordination between two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain are discussed. The purpose of this review is to summarize the regulation and dysregulation of peristalsis by the coordinated and discoordinated function of circular and longitudinal muscle layers in health and diseased states.

  15. Prognostic significance of low skeletal muscle mass compared with protein-energy malnutrition in liver cirrhosis.

    Science.gov (United States)

    Nishikawa, Hiroki; Enomoto, Hirayuki; Ishii, Akio; Iwata, Yoshinori; Miyamoto, Yuho; Ishii, Noriko; Yuri, Yukihisa; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Iijima, Hiroko; Nishiguchi, Shuhei

    2017-09-01

    To investigate the impact of low skeletal muscle mass (LSMM) on survival as compared with protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). A total of 206 individuals with LC were analyzed. We retrospectively examined the impact of LSMM, as defined by psoas muscle mass at the third lumber on computed tomography, on survival as compared with PEM. In terms of comparison of the effects of LSMM and PEM on survival, we used time-dependent receiver operating characteristics (ROC) analysis. Our study cohort included 115 men and 91 women with a median age of 67 years. There were 140 patients with Child-Pugh A, 62 with Child-Pugh B, and 4 with Child-Pugh C. A total of 117 patients (56.8%) had LSMM and 52 patients (25.2%) had PEM. The proportion of PEM in patients with LSMM (31.62%, 37/117) was significantly higher than in patients without LSMM (16.85%, 15/89) (P = 0.0229). In the multivariate analysis for the entire cohort, the presence of hepatocellular carcinoma, lower body mass index, presence of LSMM, lower triglyceride value, poorer renal function, and higher des-γ-carboxy prothrombin value were found to be significant adverse predictors linked to overall survival, while presence of PEM tended to be significant. In the time-dependent ROC analysis, all area under the ROCs for survival in LSMM at each time point were higher than those in PEM except for Child-Pugh B patients. In this comparison of LSMM and PEM on clinical outcomes in LC patients, it was shown that LSMM may have stronger prognostic impact than PEM. © 2016 The Japan Society of Hepatology.

  16. The Effect of a 12-Week Omega-3 Supplementation on Body Composition, Muscle Strength and Physical Performance in Elderly Individuals with Decreased Muscle Mass

    Directory of Open Access Journals (Sweden)

    Roma Krzymińska-Siemaszko

    2015-08-01

    Full Text Available The aim of the study was to assess the effect of a polyunsaturated omega-3 fatty acids (PUFA supplementation on the parameters of body composition, muscle strength and physical performance in elderly people with decreased muscle mass (DMM. Fifty three elderly people with an ALM index (the ratio of appendicular lean mass to squared height either below (−2SD: low muscle mass-LMM or between (−1SD and −2SD: the risk of LMM-rLMM the ALM index for the young Polish reference population were randomly assigned to PUFA-treated groups (LMM-PUFA, rLMM-PUFA or control groups (LMM-control, rLMM-control. PUFA-treated groups received capsules containing 1.3 g of PUFA and 10 mg of vitamin E, while the control groups received 11 mg of vitamin E daily for 12 weeks. Body composition (BIA analysis, muscle strength (hand grip measured with dynamometer and physical performance (Timed Up and Go test-TUG were assessed before and after supplementation. No statistically significant differences were observed either in muscle mass or in the hand grip and TUG in any group. The post-pre difference (mean ± SD in ALM index was as follows (kg/m2: LMM-PUFA: 0.00 ± 0.30, rLMM-PUFA: 0.00 ± 0.22, LMM-control: 0.03 ± 0.36, rLMM-control: –0.03 ± 0.20. In our study, a 12 week supplementation of PUFA did not affect the evaluated parameters in elderly individuals with DMM.

  17. Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Hidetaka Hamasaki

    2015-05-01

    Full Text Available Background. Age-related loss of muscle mass (sarcopenia increases the incidence of obesity in the elderly by reducing physical activity. This sarcopenic obesity may become self-perpetuating, increasing the risks for metabolic syndrome, disability, and mortality. We investigated the associations of two sarcopenic indices, the ratio of lower extremity muscle mass to body weight (L/W ratio and the ratio of lower extremity muscle mass to upper extremity muscle mass (L/U ratio, with metabolic parameters related to obesity in patients with type 2 diabetes and obesity.Methods. Of 148 inpatients with type 2 diabetes treated between October 2013 and April 2014, we recruited 26 with obesity but no physical disability. Daily physical activity was measured by a triaxial accelerometer during a period of hospitalization, and which was also evaluated by our previously reported non-exercise activity thermogenesis questionnaire. We measured body composition by bioelectrical impedance and investigated the correlations of L/W and L/U ratios with body weight, body mass index (BMI, waist circumference (WC, waist-to-hip ratio (WHR, visceral fat area, subcutaneous fat area, serum lipid profile, and daily physical activity.Results. The L/W ratio was significantly and negatively correlated with BMI, WC, WHR, body fat mass, body fat percentage, subcutaneous fat area, and serum free fatty acid concentration, was positively correlated with daily physical activity: the locomotive non-exercise activity thermogenesis score, but was not correlated with visceral fat area. The L/U ratio was significantly and positively correlated with serum high-density lipoprotein cholesterol.Conclusions. High L/W and L/U ratios, indicative of relatively preserved lower extremity muscle mass, were predictive of improved metabolic parameters related to obesity. Preserved muscle fitness in obesity, especially of the lower extremities, may prevent sarcopenic obesity and lower associated risks for

  18. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

    Directory of Open Access Journals (Sweden)

    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  19. Low skeletal muscle mass outperforms the Charlson Comorbidity Index in risk prediction in patients undergoing pancreatic resections.

    Science.gov (United States)

    Wagner, D; Marsoner, K; Tomberger, A; Haybaeck, J; Haas, J; Werkgartner, G; Cerwenka, H; Bacher, H; Mischinger, H J; Kornprat, P

    2018-05-01

    Low skeletal muscle mass is a known predictor of morbidity and mortality in patients undergoing major pancreatic surgeries. We sought to combine low skeletal muscle mass with established risk predictors to improve their prognostic capacity for postoperative outcome and morbidity. As established parameters to predict preoperative mortality risk for patients, the ASA classification and the Charlson Comorbidity Index (CCI) were used. The Hounsfield Units Average Calculation (HUAC) was measured to define low skeletal muscle mass in 424 patients undergoing pancreatic resections for malignancies. Patients in the lowest sex-adjusted quartile for HUAC were defined as having low skeletal muscle mass (muscle wasting). Multivariable Cox regression analysis was utilized to identify preoperative risk factors associated with postoperative morbidity. Median patient age was 63 years (19-87), 47.9% patients were male, and half the cohort had multiple comorbidities (Charlson Comorbidity Index [CCI]>6, 63.2%), 30-day mortality was 5.8% (n = 25). Median HUAC was 19.78 HU (IQR: 15.94-23.54) with 145 patients (34.2%) having low skeletal muscle mass. Preoperative frailty defined by low skeletal muscle mass was associated with an increased risk for postoperative complications (OR 1.55, CI 95% 0.98-2.45, p = 0.014), and a higher 30-day mortality (HR 5.17, CI 95% 1.57-16.69, p = 0.004). With an AUC of 0.85 HUAC showed the highest predictability for 30-day mortality (CI 95% 0.78-0.91, p = 0.0001). Patients with CCI ≥6 and low skeletal muscle mass defined by the HUAC had a 9.78 higher risk of dying in the immediate postoperative phase (HR 9.78, CI 95% 2.98-12.2, p = 0.0001). Low skeletal muscle mass predicts postoperative mortality and complications best and it should be incorporated to conventional risk scores to identify high risk patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights

  20. Effects of progressive strength training on muscle mass in type 2 diabetes mellitus patients determined by computed tomography

    International Nuclear Information System (INIS)

    Cauza, E.; Strehblow, C.; Hanusch-Enserer, U.; Fasching, P.; Metz-Schimmerl, S.; Strasser, B.; Kostner, K.; Dunstan, D.; Haber, P.

    2009-01-01

    To examine the effect of a 4-month progressive strength training program on muscle and fat mass assessed by computed tomography (CT) in type 2 diabetes mellitus (T2DM) patients, and to assess the relationships of changes in muscle cross-section area (CSA) with glycaemic control. Twenty adults (mean age ± SE: 56.4 ± 0.9 a) with T2DM participated in a supervised strength training program for 4 months 3 days/week. Muscle and fat areas of the quadriceps muscle were estimated by CT volumetry before and immediately after the training. Glycaemic (HbA1c) and anthropometric (BMI, skinfolds) measurements were assessed at 0 and 4 months, respectively. After strength training, muscle strength increased significantly in all measured muscle groups. Quadriceps size (CSA of the muscle) was increased by 2.4 % (from 7.99 ± 0.3 cm 3 to 8.18 ± 0.3 cm 3 , p = 0.003) for the right extremity, 3.9 % (from 8.1 ± 0.4 cm 3 to 8.41 ± 0.5 cm 3 , p = 0.04) for the left side. Fat tissue CSA reduced from 0.66 ± 0.1 cm 3 to 0.56 ± 0.12 cm 3 for the right leg (15.3 % reduction) and from 0.58 ± 0.12 cm 3 to 0.37 ± 0.13 cm 3 for the left leg (35.8 % reduction), resulting in a mean fat CSA reduction of 24.8 %. Fat mass assessed by skin folds was significantly reduced and lean body mass was significantly increased. The change in muscle CSA was not correlated with the changes in HbA1c or muscle strength. Strength training significantly improves both muscle mass and the muscle to fat ratio in T2DM. However, changes in muscle observed with computed tomography were not related to changes observed in HbA1c with training. (author) [de

  1. Usefulness of circuit training at home for improving bone mass and muscle mass while losing fat mass in undergraduate female students.

    Science.gov (United States)

    Takahata, Yoko

    2018-05-09

    The purpose of this study was to determine whether or not circuit training at home affects the calcaneus quantitative ultrasound status as well as other indices of body composition among undergraduate female students. Forty-one adolescents were recruited (18.5 ± 0.6 years old). The stiffness index of the calcaneus, broadband ultrasound attenuation of the calcaneus, speed of sound of the calcaneus, and body frame index. This was a three-month intervention study, so the measurements were conducted at baseline, 2 months later, and 3 months later while the subjects underwent circuit training at home. The subjects were divided into two groups: namely, the exercising group and non-exercising group. In the exercising group, broadband ultrasound attenuation of the calcaneus was higher 2 months later (p = 0.033) as well as 3 months later (p = 0.036), and the speed of sound of the calcaneus was higher 3 months later (p = 0.018). In addition, the muscle mass was strongly positively correlated with the calcaneus QUS-SOS (p = 0.004), while the body fat percentage was a strongly negatively correlated with the calcaneus QUS-BUA (p = 0.043). In the non-exercising group, the stiffness index of the calcaneus was higher 2 months later (p = 0.002) as well as 3 months later (p = 0.002). Furthermore, the body percentage was strongly positively correlated with the calcaneus QUS-SI (p = 0.009). These findings suggest that the calcaneus quantitative ultrasound status and muscle mass while losing fat mass may be improved by means of a simple exercise regimen within a short period among undergraduate female students.

  2. Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence.

    Science.gov (United States)

    Tezze, Caterina; Romanello, Vanina; Desbats, Maria Andrea; Fadini, Gian Paolo; Albiero, Mattia; Favaro, Giulia; Ciciliot, Stefano; Soriano, Maria Eugenia; Morbidoni, Valeria; Cerqua, Cristina; Loefler, Stefan; Kern, Helmut; Franceschi, Claudio; Salvioli, Stefano; Conte, Maria; Blaauw, Bert; Zampieri, Sandra; Salviati, Leonardo; Scorrano, Luca; Sandri, Marco

    2017-06-06

    Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of FGF21 compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kurinami, Noboru; Sugiyama, Seigo; Morita, Ayami; Yoshida, Akira; Hieshima, Kunio; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouch, Katsunori; Jinnouchi, Tomio; Jinnouchi, Hideaki

    2018-05-01

    Obesity and ectopic fat accumulation are important conditions of type 2 diabetes mellitus (T2DM). Our aim was to determine whether bioelectrical impedance body composition analysis combined with blood test results could estimate liver ectopic fat accumulation in patients with treatment-naïve T2DM. Subjects were 119 untreated T2DM patients. Computed tomography scans were performed to calculate the liver to spleen attenuation ratio (L/S ratio) as a measure of liver fat accumulation, with excess liver fat accumulation defined as an L/S ratio analysis using InBody770. The Nagelkerke R 2 test showed that the muscle mass/fat mass ratio (muscle/fat ratio) was the most suitable variable among anthropometric factors and body component indexes for estimating liver fat accumulation. The muscle/fat ratio was significantly correlated with the L/S ratio (ρ = 0.4386, P analysis showed that the muscle/fat ratio (odds ratio 0.40, 95% confidence interval 0.22-0.73, P ratio 1.06, 95% confidence interval 1.02-1.10, P analysis, the cutoff value of the muscle/fat ratio for excess liver fat accumulation was 2.34. In patients with treatment-naïve T2DM, the muscle/fat ratio and ALT are useful for estimating the presence of excess liver fat accumulation in daily clinical practice. Copyright © 2018. Published by Elsevier B.V.

  4. Effects of exercise improves muscle strength and fat mass in patients with high fracture risk: A randomized control trial

    Directory of Open Access Journals (Sweden)

    Ding-Cheng Chan

    2018-07-01

    Full Text Available Background: The deterioration of the musculoskeletal system imposes significant impact on physical activity. Exercise is an important strategy which minimizes these changes. It is not clear which type of exercise provides better improvement on low physical performance, low muscle mass and low strength of sarcopenia. We aim to develop an integrated care (IC model and compare its relative efficacy in limb fat free mass, muscle strength, and physical performance with low extremities exercise (LEE in community dwelling older adults with high risk of fractures (Fracture Risk Assessment Tool (FRAX® ≧3% for hip fracture, ≧20% for major osteoporotic fracture or 1-min osteoporosis risk test (≧1 point or fall (≧2 falls in previous year. Methods: Patients were assigned randomized to participate in either IC or LEE group (n = 55 each for 3 months. All participants received education including home-based exercise. The IC group consisted of different modalities of exercise while the LEE group performed machine-based low extremities exercise. Fat free mass, muscle strength, and physical performance were measured at their baseline and 3-months follow-up. Results: Mean age was 73.8 ± 7 years with 69.1% women. Entire cohort demonstrated significant increment in fat free mass, muscle strength (4 indicators and physical performance (3 indicators. However, between group differences were not significant. Conclusion: With regular supervise exercise; both groups are equally effective in decreasing fat mass and increasing physical performance, muscle mass and strength. However, the IC group required fewer resources and thus more financially feasible in a community setting. Keywords: Bone mineral density, Gender differences, Integrated care, Low extremities exercise, Muscle strength

  5. Catch-slip bonds can be dispensable for motor force regulation during skeletal muscle contraction

    Science.gov (United States)

    Dong, Chenling; Chen, Bin

    2015-07-01

    It is intriguing how multiple molecular motors can perform coordinated and synchronous functions, which is essential in various cellular processes. Recent studies on skeletal muscle might have shed light on this issue, where rather precise motor force regulation was partly attributed to the specific stochastic features of a single attached myosin motor. Though attached motors can randomly detach from actin filaments either through an adenosine triphosphate (ATP) hydrolysis cycle or through "catch-slip bond" breaking, their respective contribution in motor force regulation has not been clarified. Here, through simulating a mechanical model of sarcomere with a coupled Monte Carlo method and finite element method, we find that the stochastic features of an ATP hydrolysis cycle can be sufficient while those of catch-slip bonds can be dispensable for motor force regulation.

  6. Polymorphisms of muscle genes are associated with bone mass and incident osteoporotic fractures in Caucasians

    DEFF Research Database (Denmark)

    Harsløf, Torben; Frost, M; Nielsen, T L

    2013-01-01

    The interaction between muscle and bone is complex. The aim of this study was to investigate if variations in the muscle genes myostatin (MSTN), its receptor (ACVR2B), myogenin (MYOG), and myoD1 (MYOD1) were associated with fracture risk, bone mineral density (BMD), bone mineral content (BMC......), and lean body mass. We analyzed two independent cohorts: the Danish Osteoporosis Prevention Study (DOPS), comprising 2,016 perimenopausal women treated with hormone therapy or not and followed for 10 years, and the Odense Androgen Study (OAS), a cross-sectional, population-based study on 783 men aged 20......-29 years. Nine tag SNPs in the four genes were investigated. In the DOPS, individuals homozygous for the variant allele of the MSTN SNP rs7570532 had an increased risk of any osteoporotic fracture, with an HR of 1.82 (95 % CI 1.15-2.90, p = 0.01), and of nonvertebral osteoporotic fracture, with an HR of 2...

  7. The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation.

    Science.gov (United States)

    Collu-Marchese, Melania; Shuen, Michael; Pauly, Marion; Saleem, Ayesha; Hood, David A

    2015-05-19

    The ATP demand required for muscle development is accommodated by elevations in mitochondrial biogenesis, through the co-ordinated activities of the nuclear and mitochondrial genomes. The most important transcriptional activator of the mitochondrial genome is mitochondrial transcription factor A (Tfam); however, the regulation of Tfam expression during muscle differentiation is not known. Thus, we measured Tfam mRNA levels, mRNA stability, protein expression and localization and Tfam transcription during the progression of muscle differentiation. Parallel 2-fold increases in Tfam protein and mRNA were observed, corresponding with 2-3-fold increases in mitochondrial content. Transcriptional activity of a 2051 bp promoter increased during this differentiation period and this was accompanied by a 3-fold greater Tfam mRNA stabilization. Interestingly, truncations of the promoter at 1706 bp, 978 bp and 393 bp promoter all exhibited 2-3-fold higher transcriptional activity than the 2051 bp construct, indicating the presence of negative regulatory elements within the distal 350 bp of the promoter. Activation of AMP kinase augmented Tfam transcription within the proximal promoter, suggesting the presence of binding sites for transcription factors that are responsive to cellular energy state. During differentiation, the accumulating Tfam protein was progressively distributed to the mitochondrial matrix where it augmented the expression of mtDNA and COX (cytochrome c oxidase) subunit I, an mtDNA gene product. Our data suggest that, during muscle differentiation, Tfam protein levels are regulated by the availability of Tfam mRNA, which is controlled by both transcription and mRNA stability. Changes in energy state and Tfam localization also affect Tfam expression and action in differentiating myotubes. © 2015 Authors.

  8. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower muscle...... mass. Twenty young controls, (20-35 yr), 20 healthy elderly subjects (65-80 yr) and 16 elderly patients with type 2 diabetes (65-80 yr) were included in a cross sectional study. Plasma levels of TNF-alpha and IL-6 were measured after an overnight fast. Dual-energy X-ray absorptiometry and total body...... potassium counting measured truncal fat, appendicular skeletal muscle mass (ASM) and body cell mass (BCM), respectively. TNF-alpha, IL-6 and the relative truncal fat mass were higher in elderly compared with young controls. ASM was lower in diabetic men than in young controls and BCM was lower in elderly...

  9. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Science.gov (United States)

    Petrie, Michael A; Kimball, Amy L; McHenry, Colleen L; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K

    2016-01-01

    Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p muscle contraction. Vibration induced FOXK2 (p muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.

  10. Testosterone therapy increased muscle mass and lipid oxidation in aging men

    DEFF Research Database (Denmark)

    Frederiksen, Louise; Højlund, Kurt; Hougaard, David M

    2011-01-01

    The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids...... lipid oxidation (b = 5.65 mg/min/m(2), p = 0.045) increased and basal glucose oxidation (b = -9.71 mg/min/m(2), p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b = -0.01mg/min/m(2), p = 0.......92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique....

  11. Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2013-09-03

    Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

  12. Muscle quality, aerobic fitness and fat mass predict lower-extremity physical function in community-dwelling older adults.

    Science.gov (United States)

    Misic, Mark M; Rosengren, Karl S; Woods, Jeffrey A; Evans, Ellen M

    2007-01-01

    Muscle mass, strength and fitness play a role in lower-extremity physical function (LEPF) in older adults; however, the relationships remain inadequately characterized. This study aimed to examine the relationships between leg mineral free lean mass (MFLM(LEG)), leg muscle quality (leg strength normalized for MFLM(LEG)), adiposity, aerobic fitness and LEPF in community-dwelling healthy elderly subjects. Fifty-five older adults (69.3 +/- 5.5 years, 36 females, 19 males) were assessed for leg strength using an isokinetic dynamometer, body composition by dual energy X-ray absorptiometry and aerobic fitness via a treadmill maximal oxygen consumption test. LEPF was assessed using computerized dynamic posturography and stair ascent/descent, a timed up-and-go task and a 7-meter walk with and without an obstacle. Muscle strength, muscle quality and aerobic fitness were similarly correlated with static LEPF tests (r range 0.27-0.40, p < 0.05); however, the strength of the independent predictors was not robust with explained variance ranging from 9 to 16%. Muscle quality was the strongest correlate of all dynamic LEPF tests (r range 0.54-0.65, p < 0.001). Using stepwise linear regression analysis, muscle quality was the strongest independent predictor of dynamic physical function explaining 29-42% of the variance (p < 0.001), whereas aerobic fitness or body fat mass explained 5-6% of the variance (p < 0.05) depending on performance measure. Muscle quality is the most important predictor, and aerobic fitness and fat mass are secondary predictors of LEPF in community-dwelling older adults. These findings support the importance of exercise, especially strength training, for optimal body composition, and maintenance of strength and physical function in older adults.

  13. The Role of Muscle Mass, Muscle Quality, and Body Composition in Risk for the Metabolic Syndrome and Functional Decline in Older Adults: Topical Collection on Nutrition, Obesity, and Diabetes

    NARCIS (Netherlands)

    R.T. Mankowski (Robert T.); S.D. Anton (Stephen D.); M. Aubertin-Leheudre (Mylene)

    2015-01-01

    textabstractAbstract Age-related body composition changes include both loss of muscle mass (sarcopenia) and increase in fat mass, which jointly contribute to a decline in metabolic functions. Muscle quality is positively related to functional capacity and a lower risk for the development of the

  14. Normal Weight but Low Muscle Mass and Abdominally Obese: Implications for the Cardiometabolic Risk Profile in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Beijers, Rosanne J H C G; van de Bool, Coby; van den Borst, Bram; Franssen, Frits M E; Wouters, Emiel F M; Schols, Annemie M W J

    2017-06-01

    It is well established that low muscle mass affects physical performance in chronic obstructive pulmonary disease (COPD). We hypothesize that combined low muscle mass and abdominal obesity may also adversely influence the cardiometabolic risk profile in COPD, even in those with normal weight. The cardiometabolic risk profile and the responsiveness to 4 months high-intensity exercise training was assessed in normal-weight patients with COPD with low muscle mass stratified by abdominal obesity. This is a cross-sectional study including 81 clinically stable patients with COPD (age 62.5 ± 8.2 years; 50.6% males; forced expiratory volume in 1 second 55.1 ± 19.5 percentage predicted) with fat-free mass index risk profile. Triglycerides showed a significant decrease, while the HOMA-IR increased. Abdominal obesity is highly prevalent in normal-weight patients with COPD with low muscle mass who showed an increased cardiometabolic risk compared with patients without abdominal obesity. This cardiometabolic risk profile was not altered after 4 months of exercise training. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  15. Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Quistorff, Bjørn

    2008-01-01

    ADP is generally accepted as a key regulator of oxygen consumption both in isolated mitochondria and in permeabilized fibers from skeletal muscle. The present study explored inorganic phosphate in a similar regulatory role. Saponin permeabilized fibers and isolated mitochondria from type-I and type...

  16. Contribution of Heritability and Epigenetic Factors to Skeletal Muscle Mass Variation in United Kingdom Twins.

    Science.gov (United States)

    Livshits, Gregory; Gao, Fei; Malkin, Ida; Needhamsen, Maria; Xia, Yudong; Yuan, Wei; Bell, Christopher G; Ward, Kirsten; Liu, Yuan; Wang, Jun; Bell, Jordana T; Spector, Tim D

    2016-06-01

    Skeletal muscle mass (SMM) is one of the major components of human body composition, with deviations from normal values often leading to sarcopenia. Our major aim was to conduct a genome-wide DNA methylation study in an attempt to identify potential genomic regions associated with SMM. This was a mixed cross-sectional and longitudinal study. Community-based study. A total of 1550 middle-aged United Kingdom twins (monozygotic [MZ] and dizygotic [DZ]), 297 of which were repeatedly measured participated in the study. Appendicular lean mass assessed using dual-energy X-ray absorptiometry technology, and methylated DNA immunoprecipitation sequencing DNA methylation profiling genome-wide were obtained from each individual. Heritability estimate of SMM, with simultaneous adjustment for covariates obtained using variance decomposition analysis, was h(2) = 0.809 ± 0.050. After quality control and analysis of longitudinal stability, the DNA methylation data comprised of 723 029 genomic sites, with positive correlations between repeated measurements (Rrepeated = 0.114-0.905). Correlations between MZ and DZ twins were 0.51 and 0.38 at a genome-wide average, respectively, and clearly increased with Rrepeated. Testing for DNA methylation association with SMM in 50 discordant MZ twins revealed 36 081 nominally significant results, of which the top-ranked 134 signals (P 0.40) were subjected to replication in the sample of 1196 individuals. Seven SMM methylation association signals replicated at a false discovery rate less than 0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, and ZFP64, which have previously been highlighted in muscle-related studies. Adjusting for age, smoking, and blood cell heterogeneity did not alter significance of these associations. This epigenome-wide study, testing longitudinally stable methylation sites, discovered and replicated a number of associations between DNA methylation at CpG loci and SMM. Four replicated signals were

  17. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

    Directory of Open Access Journals (Sweden)

    Kenneth M Baldwin

    2013-10-01

    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  18. Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis: Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use.

    Science.gov (United States)

    Yamada, Shunsuke; Tsuruya, Kazuhiko; Yoshida, Hisako; Tokumoto, Masanori; Ueki, Kenji; Ooboshi, Hiroaki; Kitazono, Takanari

    2016-07-01

    Myostatin is a member of the transforming growth factor-β family, which regulates synthesis and degradation of skeletal muscle proteins and is associated with the development of sarcopenia. It is up-regulated in the skeletal muscle of chronic kidney disease patients and is considered to be involved in the development of uremic sarcopenia. However, serum myostatin levels have rarely been determined, and the relationship between serum myostatin levels with clinical and metabolic factors remains unknown. This cross-sectional study investigated the association between serum myostatin level and clinical factors in 69 outpatients undergoing peritoneal dialysis. Serum myostatin level was determined by commercially available enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable analysis were conducted to determine factors associated with serum myostatin levels. The factors included age, sex, diabetes mellitus, dialysis history, body mass index, residual kidney function, peritoneal dialysate volume, serum biochemistries, and the use of vitamin D receptor activators (VDRAs). Mean serum myostatin level was 7.59 ± 3.37 ng/mL. There was no association between serum myostatin level and residual kidney function. Serum myostatin levels were significantly and positively associated with lean body mass measured by the creatinine kinetic method and negatively associated with the use of VDRAs after adjustment for potential confounding factors. Our study indicated that serum myostatin levels are associated with skeletal muscle mass and are lower in patients treated with VDRAs. Further studies are necessary to determine the significance of measuring serum myostatin level in patients undergoing peritoneal dialysis.

  19. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

    Science.gov (United States)

    Shiba, Naoto; Matsuse, Hiroo; Takano, Yoshio; Yoshimitsu, Kazuhiro; Omoto, Masayuki; Hashida, Ryuki; Tagawa, Yoshihiko; Inada, Tomohisa; Yamada, Shin; Ohshima, Hiroshi

    2015-01-01

    Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS). We developed the Hybrid Training System (HTS) to maintain an astronaut's musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system's orbital operation capability and utility, as well as its preventative effect on an astronaut's musculoskeletal atrophy. HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR). 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks) were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance), MRI (muscle volume), and DXA (BMD, lean [muscle] mass, fat mass). Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force) and a measuring tape (upper arm circumference). The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm) changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule) of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts) of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle) mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR. These results showed the orbital operation

  20. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

    Directory of Open Access Journals (Sweden)

    Naoto Shiba

    Full Text Available Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS. We developed the Hybrid Training System (HTS to maintain an astronaut's musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system's orbital operation capability and utility, as well as its preventative effect on an astronaut's musculoskeletal atrophy.HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR. 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance, MRI (muscle volume, and DXA (BMD, lean [muscle] mass, fat mass. Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force and a measuring tape (upper arm circumference.The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR.These results showed the orbital

  1. Rac1 governs exercise‐stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

    Science.gov (United States)

    Nielsen, Ida L.; Kleinert, Maximilian; Møller, Lisbeth L. V.; Ploug, Thorkil; Schjerling, Peter; Bilan, Philip J.; Klip, Amira; Jensen, Thomas E.; Richter, Erik A.

    2016-01-01

    Key point Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood.The GTPase Rac1 can be activated by muscle contraction and has been found to be necessary for insulin‐stimulated glucose uptake, although its role in exercise‐stimulated glucose uptake is unknown.We show that Rac1 regulates the translocation of the glucose transporter GLUT4 to the plasma membrane in skeletal muscle during exercise.We find that Rac1 knockout mice display significantly reduced glucose uptake in skeletal muscle during exercise. Abstract Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood. Despite extensive efforts, the signalling mechanisms vital for glucose uptake during exercise are not yet fully understood, although the GTPase Rac1 is a candidate molecule. The present study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise‐induced uptake of radiolabelled 2‐deoxyglucose at 65% of maximum running capacity was blocked in soleus muscle and decreased by 80% and 60% in gastrocnemius and tibialis anterior muscles, respectively, in muscle‐specific inducible Rac1 knockout (mKO) mice compared to wild‐type littermates. By developing an assay to quantify endogenous GLUT4 translocation, we observed that GLUT4 content at the sarcolemma in response to exercise was reduced in Rac1 mKO muscle. Our findings implicate Rac1 as a regulatory element critical for controlling glucose uptake during exercise via regulation of GLUT4 translocation. PMID:27061726

  2. Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice.

    Science.gov (United States)

    Ohno, Y; Egawa, T; Yokoyama, S; Nakai, A; Sugiura, T; Ohira, Y; Yoshioka, T; Goto, K

    2015-12-01

    Effects of heat shock transcription factor 1 (HSF1) deficiency on heat stress-associated increase in slow soleus muscle mass of mice were investigated. Both HSF1-null and wild-type mice were randomly assigned to control and heat-stressed groups. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anaesthesia. Significant increase in wet and dry weights, and protein content of soleus muscle in wild-type mice was observed seven days after the application of the heat stress. However, heat stress had no impact on soleus muscle mass in HSF1-null mice. Neither type of mice exhibited much effect of heat stress on HSF mRNA expression (HSF1, HSF2 and HSF4). On the other hand, heat stress upregulated heat shock proteins (HSPs) at the mRNA (HSP72) and protein (HSP72 and HSP110) levels in wild-type mice, but not in HSF1-null mice. The population of Pax7-positive nuclei relative to total myonuclei of soleus muscle in wild-type mice was significantly increased by heat stress, but not in HSF1-null mice. Furthermore, the absence of HSF1 gene suppressed heat stress-associated phosphorylation of Akt and p70 S6 kinase (p-p70S6K) in soleus muscle. Heat stress-associated increase in skeletal muscle mass may be induced by HSF1 and/or HSF1-mediated stress response that activates muscle satellite cells and Akt/p70S6K signalling pathway. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  3. Effects of exercise improves muscle strength and fat mass in patients with high fracture risk: A randomized control trial.

    Science.gov (United States)

    Chan, Ding-Cheng; Chang, Chirn-Bin; Han, Der-Sheng; Hong, Cian-Hui; Hwang, Jawl-Shan; Tsai, Keh-Sung; Yang, Rong-Sen

    2017-10-26

    The deterioration of the musculoskeletal system imposes significant impact on physical activity. Exercise is an important strategy which minimizes these changes. It is not clear which type of exercise provides better improvement on low physical performance, low muscle mass and low strength of sarcopenia. We aim to develop an integrated care (IC) model and compare its relative efficacy in limb fat free mass, muscle strength, and physical performance with low extremities exercise (LEE) in community dwelling older adults with high risk of fractures (Fracture Risk Assessment Tool (FRAX ® )) ≧3% for hip fracture, ≧20% for major osteoporotic fracture or 1-min osteoporosis risk test (≧1 point) or fall (≧2 falls in previous year). Patients were assigned randomized to participate in either IC or LEE group (n = 55 each) for 3 months. All participants received education including home-based exercise. The IC group consisted of different modalities of exercise while the LEE group performed machine-based low extremities exercise. Fat free mass, muscle strength, and physical performance were measured at their baseline and 3-months follow-up. Mean age was 73.8 ± 7 years with 69.1% women. Entire cohort demonstrated significant increment in fat free mass, muscle strength (4 indicators) and physical performance (3 indicators). However, between group differences were not significant. With regular supervise exercise; both groups are equally effective in decreasing fat mass and increasing physical performance, muscle mass and strength. However, the IC group required fewer resources and thus more financially feasible in a community setting. Copyright © 2017. Published by Elsevier B.V.

  4. Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle

    DEFF Research Database (Denmark)

    Holst, Dorte; Luquet, Serge; Nogueira, Véronique

    2003-01-01

    starvation period, PPARdelta mRNA levels are dramatically up-regulated in gastrocnemius muscle of mice and restored to control level upon refeeding. The rise of PPARdelta is accompanied by parallel up-regulations of fatty acid translocase/CD36 (FAT/CD36) and heart fatty acid binding protein (H-FABP), while...

  5. Adaptive force regulation of muscle strengthening rehabilitation device with magnetorheological fluids.

    Science.gov (United States)

    Dong, Shufang; Lu, Ke-Qian; Sun, Jian Qiao; Rudolph, Katherine

    2006-03-01

    In rehabilitation from neuromuscular trauma or injury, strengthening exercises are often prescribed by physical therapists to recover as much function as possible. Strengthening equipment used in clinical settings range from low-cost devices, such as sandbag weights or elastic bands to large and expensive isotonic and isokinetic devices. The low-cost devices are incapable of measuring strength gains and apply resistance based on the lowest level of torque that is produced by a muscle group. Resistance that varies with joint angle can be achieved with isokinetic devices in which angular velocity is held constant and variable torque is generated when the patient attempts to move faster than the device but are ineffective if a patient cannot generate torque rapidly. In this paper, we report the development of a versatile rehabilitation device that can be used to strengthen different muscle groups based on the torque generating capability of the muscle that changes with joint angle. The device is low cost, is smaller than other commercially available machines, and can be programmed to apply resistance that is unique to a particular patient and that will optimize strengthening. The core of the device, a damper with smart magnetorheological fluids, provides passive exercise force. A digital adaptive control is capable of regulating exercise force precisely following the muscle strengthening profile prescribed by a physical therapist. The device could be programmed with artificial intelligence to dynamically adjust the target force profile to optimize rehabilitation effects. The device provides both isometric and isokinetic strength training and can be developed into a small, low-cost device that may be capable of providing optimal strengthening in the home.

  6. Low vitamin D status is associated with reduced muscle mass and impaired physical performance in frail elderly people

    NARCIS (Netherlands)

    Tieland, C.A.B.; Brouwer, E.M.; Nienaber-Rousseau, C.; Loon, van L.J.C.; Groot, de C.P.G.M.

    2013-01-01

    Background/Objectives: Serum 25-hydroxyvitamin D (25(OH)D) status has been associated with muscle mass, strength and physical performance in healthy elderly people. Yet, in pre-frail and frail elderly people this association has not been studied. The objective of this study was to explore the

  7. The impact of dietary protein or amino acid supplementation on muscle mass and strength in elderly people

    NARCIS (Netherlands)

    Tieland, M.; Franssen, R.; Dullemeijer, C.; Dronkelaar, van C.; Kim, H.K.; Ispoglou, T.; Zhu, K.; Prince, R.L.; Loon, van L.J.C.; Groot, de Lisette C.P.G.M.

    2017-01-01

    Objectives: Increasing protein or amino acid intake has been promoted as a promising strategy to increase muscle mass and strength in elderly people, however, long-term intervention studies show inconsistent findings. Therefore, we aim to determine the impact of protein or amino acid

  8. Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract

    NARCIS (Netherlands)

    J.L.A. van Vugt (Jeroen); S. Büttner (Stefan); S. Levolger (S.); R.R.J. Coebergh van den Braak (Robert); M. Suker (Mustafa); M.P. Gaspersz (Marcia); R.W.F. de Bruin (Ron); C. Verhoef (Kees); Van Eijck, C.H.C. (Casper H. C.); Bossche, N. (Niek); B. Groot Koerkamp (Bas); J.N.M. IJzermans (Jan)

    2017-01-01

    textabstractBackground: Low skeletal muscle mass is associated with poor postoperative outcomes in cancer patients. Furthermore, it is associated with increased healthcare costs in the United States. We investigated its effect on hospital expenditure in a Western-European healthcare system, with

  9. Basic Training of Student’s Outdoor Club Increases Muscle Mass after Five Weeks of Exercise in Males

    Directory of Open Access Journals (Sweden)

    Novie Salsabila

    2015-03-01

    Full Text Available Background: Aerobic and anaerobic exercises, may lead to increase muscle mass. The aim of this study was to determine the change in muscle mass during basic training of students’ outdoor club. Methods: This was an observational analytic study to college students who joined basic training of students’ outdoor club for 19 weeks. Subjects consisted of 17 male and 15 female students, measured five times consecutively by using Body Fat/Hydration monitor scale, with Bioelectrical Impedance Analysis principle. Data collection was performed five times, from February to July 2012 in Bandung. Statistical analysis was processed using Analysis of Variance (ANOVA. Results: The result in males showed the mean 43.35±3.15 on the initial measurement. The muscle mass further increased significantly after five, ten, fifteen, and nineteen weeks of exercise (43.73±3.18 (p0.05; 38.08±1.67 (p>0.05 ; 38.23±1.52 (p>0.05 ; 38.61±1.52 (p<0.05 vs 37.77±2.00 respectively. Conclusion: Basic training of student’s outdoor club increases muscle mass significantly after five weeks of exercise in males, but not in females

  10. Effects of exercise training on regulation of skeletal muscle glucose metabolism in elderly men

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup; Olesen, Jesper; Gliemann, Lasse

    2015-01-01

    glucose tolerance test (OGTT) and a muscle biopsy was obtained from the vastus lateralis before and 45 minutes into the OGTT. Blood samples were collected before and up to 120 minutes after glucose intake. RESULTS: Exercise training increased Hexokinase II, GLUT4, Akt2, glycogen synthase (GS), pyruvate......) phosphorylation was increased after exercise training. In the trained state, the PDHa activity was reduced following glucose intake and without changes in phosphorylation level of PDH-E1α. CONCLUSIONS: The present results suggest that exercise training improves glucose regulation in elderly subjects by enhancing......BACKGROUND: The aim was to investigate the molecular mechanisms behind exercise training-induced improvements in glucose regulation in aged subjects. METHODS: Twelve elderly male subjects completed 8 weeks of exercise training. Before and after the training period, the subjects completed an oral...

  11. Thyroid hormone regulates muscle function during cold acclimation in zebrafish (Danio rerio).

    Science.gov (United States)

    Little, Alexander G; Seebacher, Frank

    2013-09-15

    Thyroid hormone (TH) is a universal regulator of growth, development and metabolism during cold exposure in mammals. In zebrafish (Danio rerio), TH regulates locomotor performance and metabolism during cold acclimation. The influence of TH on locomotor performance may be via its effect on metabolism or, as has been shown in mammals, by modulating muscle phenotypes. Our aim was to determine whether TH influences muscle phenotypes in zebrafish, and whether this could explain changes in swimming capacity in response to thermal acclimation. We used propylthiouracil and iopanoic acid to induce hypothyroidism in zebrafish over a 3-week acclimation period to either 18 or 28°C. To verify that physiological changes following hypothyroid treatment were in fact due to the action of TH, we supplemented hypothyroid fish with 3,5-diiodothryronine (T2) or 3,5,3'-triiodothyronine (T3). Cold-acclimated fish had significantly greater sustained swimming performance (Ucrit) but not burst speed. Greater Ucrit was accompanied by increased tail beat frequency, but there was no change in tail beat amplitude. Hypothyroidism significantly decreased Ucrit and burst performance, as well as tail beat frequency and SERCA activity in cold-acclimated fish. However, myofibrillar ATPase activity increased in cold-acclimated hypothyroid fish. Hypothyroid treatment also decreased mRNA concentrations of myosin heavy chain fast isoforms and SERCA 1 isoform in cold-acclimated fish. SERCA 1 mRNA increased in warm-acclimated hypothyroid fish, and SERCA 3 mRNA decreased in both cold- and warm-acclimated hypothyroid fish. Supplementation with either T2 or T3 restored Ucrit, burst speed, tail beat frequency, SERCA activity and myosin heavy chain and SERCA 1 and 3 mRNA levels of hypothyroid fish back to control levels. We show that in addition to regulating development and metabolism in vertebrates, TH also regulates muscle physiology in ways that affect locomotor performance in fish. We suggest that the

  12. MicroRNA-761 regulates mitochondrial biogenesis in mouse skeletal muscle in response to exercise

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yanli [Affiliated Hospital of Hebei Engineering University, Handan, 056002, Hebei (China); Zhao, Chaoxian; Sun, Xuewen [Medical College of Hebei Engineering University, Handan, 056002, Hebei (China); Liu, Zhijun, E-mail: liuzhij1207@163.com [Affiliated Hospital of Hebei Engineering University, Handan, 056002, Hebei (China); Zhang, Jianzhong, E-mail: zhangjianzhong@icdc.cn [National Institute for Communicable Disease Control and Prevention (ICDC), Chinese Center for Disease Control and Prevention (China CDC), Beijing, 102206 (China)

    2015-11-06

    MicroRNAs (miRNAs) have been suggested to play critical roles in skeletal muscle in response to exercise. Previous study has shown that miR-761 was involved in a novel model regulating the mitochondrial network. However, its role in mitochondrial biogenesis remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-761 on mitochondrial biogenesis in skeletal muscle. Real-time quantitative PCR analysis demonstrated that aberrantly expressed miR-761 is involved in exercise activity and miR-761 is decreased by exercise training compared with the sedentary control mice. miR-761 suppresses mitochondrial biogenesis of C{sub 2}C{sub 12} myocytes by targeting the 3′-UTR of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1α). Overexpression of miR-761 was capable of inhibiting the protein expression levels of PGC-1α. Moreover, miR-761 overexpression suppressed the p38 MAPK signaling pathway and down-regulated the expression of phosphorylated MAPK-activated protein kinase-2 (P-MK2), a downstream kinase of p38 MAPK. The phosphorylation of activating transcription factors 2 (ATF2) that plays a functional role in linking the activation of the p38 MAPK pathway to enhanced transcription of the PGC-1α was also inhibited by the overexpression of miR-761. These findings revealed a novel regulation mechanism for miR-761 in skeletal myocytes, and contributed to a better understanding of the modulation of skeletal muscle in response to exercise. - Highlights: • Endurance exercise decreases miR-761 expression in skeletal muscle. • MiR-761 suppresses mitochondrial biogenesis in C{sub 2}C{sub 12} myocytes. • MiR-761 directly targeted PGC-1α expression. • MiR-761 suppresses p38 MAPK signaling pathways in C{sub 2}C{sub 12} myocytes. • A novel mechanism for miR-761 in skeletal myocytes is demonstrated.

  13. Measurement of Muscle Protein Fractional Synthetic Rate by Capillary Gas Chromatography/Combustion Isotope Ratio Mass Spectrometry

    Science.gov (United States)

    Yarasheski, Kevin E.; Smith, Kenneth; Rennie, Michael J.; Bier, Dennis M.

    2014-01-01

    The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague–Dawley rats after each was infused at a different rate with (1-13C)leucine for 6–8 h. Muscle leucine enrichment (at.% excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12–14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 ± 0.011% h−1 (mean ± SEM); range = 0.023–0.147% h−1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS. PMID:1420371

  14. Reference Centile Curves for Body Fat Percentage, Fat-free Mass, Muscle Mass and Bone Mass Measured by Bioelectrical Impedance in Asian Indian Children and Adolescents.

    Science.gov (United States)

    Chiplonkar, Shashi; Kajale, Neha; Ekbote, Veena; Mandlik, Rubina; Parthasarathy, Lavanya; Borade, Ashwin; Patel, Pinal; Patel, Prerna; Khadilkar, Vaman; Khadilkar, Anuradha

    2017-12-15

    To create gender-specific percentile curves for percent body fat (%BF) by Bio electrical Impedance Analysis (BIA) for screening adiposity and risk of hypertension in Indian children and generate reference curves for percent fat-free mass (%FFM), muscle mass (%LM) and bone mineral content (BMC) by using bioelectrical impedance. Secondary analysis of data from previous multicenter cross-sectional studies. Private schools from five regions of India. A random sample of 3850 healthy school children (2067 boys) (5-17 yr) from private schools in five major Indian cities. Anthropometry, blood pressure (BP) and body composition were measured by bioelectrical impedance. Reference curves were generated by the LMS method. %BF, %FFM, %LM, BMC and BP. Median %BF increased by 6% from 5 to 13 years of age and declined (around 2%) up to 17 years in boys. In girls, %BF increased by 8% from 5 to 14 years and thereafter declined by 3%. Based upon the risk of hypertension, the new cut-offs of 75th and 85th percentile of %BF were proposed for detecting over fatness and excess fatness in children. Median %FFM was 90% at 5 yrs and decreased till 12 years, and then showed a slight increase to 84% at 17 yrs in boys. In girls, it was 86% at 5 yrs and decreased till 15 yrs, and plateaued at 71.8% at 17 yrs. Reference curves for percent body fat for Indian children would be useful to screen children for health risk in clinical set up.

  15. Application of the principles of systems biology and Wiener's cybernetics for analysis of regulation of energy fluxes in muscle cells in vivo.

    Science.gov (United States)

    Guzun, Rita; Saks, Valdur

    2010-03-08

    The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener's cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener's cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures - intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of

  16. Application of the Principles of Systems Biology and Wiener’s Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo

    Science.gov (United States)

    Guzun, Rita; Saks, Valdur

    2010-01-01

    The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener’s cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener’s cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures – intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations

  17. MALDI imaging mass spectrometry: Discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures

    OpenAIRE

    Klein, O.; Strohschein, K.; Nebrich, G.; Oetjen, J.; Trede, D.; Thiele, H.; Alexandrov, T.; Giavalisco, P.; Duda, G.N.; Roth, P. von; Geissler, S.; Klose, J.; Winkler, T.

    2014-01-01

    Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological region...

  18. Changes in lower limb muscle function and muscle mass following exercise-based interventions in patients with chronic obstructive pulmonary disease: A review of the English-language literature.

    Science.gov (United States)

    De Brandt, Jana; Spruit, Martijn A; Hansen, Dominique; Franssen, Frits Me; Derave, Wim; Sillen, Maurice Jh; Burtin, Chris

    2018-05-01

    Chronic obstructive pulmonary disease (COPD) patients often experience lower limb muscle dysfunction and wasting. Exercise-based training has potential to improve muscle function and mass, but literature on this topic is extensive and heterogeneous including numerous interventions and outcome measures. This review uses a detailed systematic approach to investigate the effect of this wide range of exercise-based interventions on muscle function and mass. PUBMED and PEDro databases were searched. In all, 70 studies ( n = 2504 COPD patients) that implemented an exercise-based intervention and reported muscle strength, endurance, or mass in clinically stable COPD patients were critically appraised. Aerobic and/or resistance training, high-intensity interval training, electrical or magnetic muscle stimulation, whole-body vibration, and water-based training were investigated. Muscle strength increased in 78%, muscle endurance in 92%, and muscle mass in 88% of the cases where that specific outcome was measured. Despite large heterogeneity in exercise-based interventions and outcome measures used, most exercise-based trials showed improvements in muscle strength, endurance, and mass in COPD patients. Which intervention(s) is (are) best for which subgroup of patients remains currently unknown. Furthermore, this literature review identifies gaps in the current knowledge and generates recommendations for future research to enhance our knowledge on exercise-based interventions in COPD patients.

  19. Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression.

    Science.gov (United States)

    Rossi, Giuliana; Antonini, Stefania; Bonfanti, Chiara; Monteverde, Stefania; Vezzali, Chiara; Tajbakhsh, Shahragim; Cossu, Giulio; Messina, Graziella

    2016-03-08

    Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Muscle strength and regional lean body mass influence on mineral bone health in young male adults.

    Science.gov (United States)

    Guimarães, Bianca Rosa; Pimenta, Luciana Duarte; Massini, Danilo Alexandre; Dos Santos, Daniel; Siqueira, Leandro Oliveira da Cruz; Simionato, Astor Reis; Dos Santos, Luiz Gustavo Almeida; Neiva, Cassiano Merussi; Pessôa Filho, Dalton Muller

    2018-01-01

    The relationship between muscle strength and bone mineral content (BMC) and bone mineral density (BMD) is supposed from the assumption of the mechanical stress influence on bone tissue metabolism. However, the direct relationship is not well established in younger men, since the enhancement of force able to produce effective changes in bone health, still needs to be further studied. This study aimed to analyze the influence of muscle strength on BMC and BMD in undergraduate students. Thirty six men (24.9 ± 8.6 y/o) were evaluated for regional and whole-body composition by dual energy X-ray absorptiometry (DXA). One repetition maximum tests (1RM) were assessed on flat bench-press (BP), lat-pull down (LPD), leg-curl (LC), knee extension (KE), and leg-press 45° (LP45) exercises. Linear regression modelled the relationships of BMD and BMC to the regional body composition and 1RM values. Measurements of dispersion and error (R2adj and standard error of estimate (SEE)) were tested, setting ρ at ≤0.05. The BMD mean value for whole-body was 1.12±0.09 g/cm2 and BMC attained 2477.9 ± 379.2 g. The regional lean mass (LM) in upper-limbs (UL) (= 6.80±1.21 kg) was related to BMC and BMD for UL (R2adj = 0.74, pBMC and BMD for LL (R2adj = 0.68, pBMC (R2adj = 0.47, pBMC (R2adj = 0.36, pBMC and BMD in young men, strengthening the relationship between force and LM, and suggesting both to parametrizes bone mineral health.

  1. Assessment of respiratory muscle strength in children according to the classification of body mass index

    Directory of Open Access Journals (Sweden)

    George Jung da Rosa

    2014-06-01

    Full Text Available OBJECTIVE: To assess and compare the respiratory muscle strength among eutrophic, overweight and obese school children, as well as to identify anthropometric and respiratory variables related to the results.METHODS: Cross-sectional survey with healthy schoolchildren aged 7-9 years old, divided into three groups: Normal weight, Overweight and Obese. The International Study of Asthma and Allergies in Childhood (ISAAC questionnaire was applied. The body mass index (BMI was evaluated, as well as the forced expiratory volume in one second (FEV1 with a portable digital device. The maximal inspiratory and expiratory pressures (MIP and MEP were measured by a digital manometer. Comparisons between the groups were made by Kruskal-Wallis test. Spearman's correlation coefficient was used to analyze the correlations among the variables.RESULTS: MIP of eutrophic school children was higher than MIP found in overweight (p=0.043 and obese (p=0.013 children. MIP was correlated with BMI percentile and weight classification (r=-0.214 and r=-0.256 and MEP was correlated with height (r=0.328. Both pressures showed strong correlation with each other in all analyses (r≥0.773, and less correlation with FEV1 (MIP - r=0.362 and MEP - r=0.494. FEV1 correlated with MEP in all groups (r: 0.429 - 0.569 and with MIP in Obese Group (r=0.565. Age was correlated with FEV1 (r=0.578, MIP (r=0.281 and MEP (r=0.328.CONCLUSIONS: Overweight and obese children showed lower MIP values, compared to eutrophic ones. The findings point to the influence of anthropometric variables on respiratory muscle strength in children.

  2. What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and Function.

    Science.gov (United States)

    Glass, David J

    2017-08-01

    In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Impact of Weight Loss on Physical Function with Changes in Strength, Muscle Mass, and Muscle Fat Infiltration in Overweight to Moderately Obese Older Adults: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Adam J. Santanasto

    2011-01-01

    Full Text Available Purpose. Evaluate the effects of weight loss on muscle mass and area, muscle fat infiltration, strength, and their association with physical function. Methods. Thirty-six overweight to moderately obese, sedentary older adults were randomized into either a physical activity plus weight loss (PA+WL or physical activity plus successful aging health education (PA+SA program. Measurements included body composition by dual-energy X-ray absorptiometry, computerized tomography, knee extensor strength, and short physical performance battery (SPPB. Results. At 6 months, PA+WL lost greater thigh fat and muscle area compared to PA+SA. PA+WL lost 12.4% strength; PA+SA lost 1.0%. Muscle fat infiltration decreased significantly in PA+WL and PA+SA. Thigh fat area decreased 6-fold in comparison to lean area in PA+WL. Change in total SPPB score was strongly inversely correlated with change in fat but not with change in lean or strength. Conclusion. Weight loss resulted in additional improvements in function over exercise alone, primarily due to loss of body fat.

  4. Lower Jump Power Rather Than Muscle Mass Itself is Associated with Vertebral Fracture in Community-Dwelling Elderly Korean Women.

    Science.gov (United States)

    Lee, Eun Young; Lee, Su Jin; Kim, Kyoung Min; Seo, Da Hea; Lee, Seung Won; Choi, Han Sol; Kim, Hyeon Chang; Youm, Yoosik; Kim, Chang Oh; Rhee, Yumie

    2017-06-01

    Sarcopenia is considered to be a risk factor for osteoporotic fracture, which is a major health problem in elderly women. In this study, we aimed to investigate the association of sarcopenia, with regard to muscle mass and function, with prevalent vertebral fracture in community-dwelling elderly women. We recruited 1281 women aged 64 to 87 years from the Korean Urban Rural Elderly cohort study. Muscle mass and function were measured using bioimpedance analysis and jumping mechanography. Skeletal muscle index (SMI) and jump power were used as an indicator of muscle mass and function, respectively. Among the participants, we observed 282 (18.9%) vertebral fractures and 564 (44.0%) osteoporosis. Although age, body mass index, and prevalence of osteoporosis increased as both SMI and jump power decreased, prevalence of vertebral fracture increased only when jump power decreased. In univariate analysis, compared with the highest quartile of jump power, the lowest quartile had a significant odds ratio of 2.80 (95% CI 1.79-4.36) for vertebral fracture. This association between jump power and vertebral fracture remained significant, with an odds ratio of 3.04 (95% CI 1.77-5.23), even after adjusting for other risk factors including age, bone mineral density, previous fracture, and cognitive function. In contrast, there was no association between SMI and vertebral fracture. Based on our results, low jump power, but not SMI, is associated with vertebral fracture in community-dwelling elderly Korean women. This finding suggests that jump power may have a more important role than muscle mass itself for osteoporotic fracture.

  5. Contraction-induced increases in Na+-K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Thomassen, Martin; Lundby, Carsten

    2005-01-01

    The present study tested the hypothesis that exercise with a large compared with a small active muscle mass results in a higher contraction-induced increase in Na+-K+-ATPase mRNA expression due to greater hormonal responses. Furthermore, the relative abundance of Na+-K+-ATPase subunit a1, a2, a3, a......% of the a2 expression, and no reliable detection of a3 and a4 was possible. In conclusion, activation of additional muscle mass does not result in a higher exercise-induced increase in Na+-K+-ATPase subunit-specific mRNA.......4, ß1, ß2, and ß3 mRNA in human skeletal muscle was investigated. On two occasions, eight subjects performed one-legged knee extension exercise (L) or combined one-legged knee extension and bilateral arm cranking (AL) for 5.00, 4.25, 3.50, 2.75, and 2.00 min separated by 3 min of rest. Leg exercise...

  6. Unaccustomed eccentric contractions impair plasma K+ regulation in the absence of changes in muscle Na+,K+-ATPase content.

    Directory of Open Access Journals (Sweden)

    Craig A Goodman

    Full Text Available The Na+,K+-ATPase (NKA plays a fundamental role in the regulation of skeletal muscle membrane Na+ and K+ gradients, excitability and fatigue during repeated intense contractions. Many studies have investigated the effects of acute concentric exercise on K+ regulation and skeletal muscle NKA, but almost nothing is known about the effects of repeated eccentric contractions. We therefore investigated the effects of unaccustomed maximal eccentric knee extensor contractions on K+ regulation during exercise, peak knee extensor muscle torque, and vastus lateralis muscle NKA content and 3-O-MFPase activity. Torque measurements, muscle biopsies, and venous blood samples were taken before, during and up to 7 days following the contractions in six healthy adults. Eccentric contractions reduced peak isometric muscle torque immediately post-exercise by 26±11% and serum creatine kinase concentration peaked 24 h post-exercise at 339±90 IU/L. During eccentric contractions, plasma [K+] rose during Set 1 and remained elevated at ∼4.9 mM during sets 4-10; this was despite a decline in work output by Set 4, which fell by 18.9% at set 10. The rise in plasma [K+] x work(-1 ratio was elevated over Set 2 from Set 4- Set 10. Eccentric contractions had no effect on muscle NKA content or maximal in-vitro 3-O-MFPase activity immediately post- or up to 7 d post-exercise. The sustained elevation in plasma [K+] despite a decrease in work performed by the knee extensor muscles suggests an impairment in K+ regulation during maximal eccentric contractions, possibly due to increased plasma membrane permeability or to excitation-contraction uncoupling.

  7. An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes.

    Directory of Open Access Journals (Sweden)

    Heather Kirk-Ballard

    Full Text Available Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011 improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-A(y murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-A(y murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.

  8. Volume regulation in mammalian skeletal muscle: the role of sodium-potassium-chloride cotransporters during exposure to hypertonic solutions.

    Science.gov (United States)

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-06-01

    Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10-20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent on the

  9. MALDI imaging mass spectrometry: discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures.

    Science.gov (United States)

    Klein, Oliver; Strohschein, Kristin; Nebrich, Grit; Oetjen, Janina; Trede, Dennis; Thiele, Herbert; Alexandrov, Theodore; Giavalisco, Patrick; Duda, Georg N; von Roth, Philipp; Geissler, Sven; Klose, Joachim; Winkler, Tobias

    2014-10-01

    Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological regions in injured skeletal muscle is inadequate, underlying mechanisms of the beneficial effects of mesenchymal stromal cell transplantation on primary trauma and trauma adjacent muscle area remain elusive. For discrimination of these pathophysiological regions, formalin-fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using two computational evaluation strategies, a supervised approach (ClinProTools) and unsupervised segmentation (SCiLS Lab), characteristic m/z species could be assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up" MS for protein identification and validation of results by immunohistochemistry, we could identify two proteins, skeletal muscle alpha actin and carbonic anhydrase III, which discriminate between the secondary damage on adjacent tissue and the primary traumatized muscle area. Our results underscore the high potential of MALDI imaging MS to describe the spatial characteristics of pathophysiological changes in muscle. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Science.gov (United States)

    DiGirolamo, Douglas J.; Singhal, Vandana; Chang, Xiaoli; Lee, Se-Jin; Germain-Lee, Emily L.

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system. PMID:26161291

  11. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Directory of Open Access Journals (Sweden)

    Michael A Petrie

    Full Text Available Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat and mechanical stress (vibration on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.The purpose of this study is to examine whether active mechanical stress (muscle contraction, passive mechanical stress (vibration, or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus to analyze mRNA gene expression.We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold, PGC-1α (5.46 fold, and ABRA (5.98 fold; and repressed MSTN (0.56 fold. Heat stress repressed PGC-1α (0.74 fold change; p < 0.05; while vibration induced FOXK2 (2.36 fold change; p < 0.05. Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05, but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05 while heat stress repressed PGC-1α (0.74 fold and ANKRD1 genes (0.51 fold; p < 0.05.These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell

  12. Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

    Science.gov (United States)

    Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

    2017-10-01

    Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

  13. Quantitative analysis of veterinary drugs in bovine muscle and milk by liquid chromatography quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Saito-Shida, Shizuka; Sakai, Takatoshi; Nemoto, Satoru; Akiyama, Hiroshi

    2017-07-01

    A simple and reliable multiresidue method for quantitative determination of veterinary drugs in bovine muscle and milk using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was developed. Critical MS parameters such as capillary voltage, cone voltage, collision energy, desolvation gas temperature and extraction mass window were carefully optimised to obtain the best possible sensitivity. Analytical samples were prepared using extraction with acetonitrile and hexane in the presence of anhydrous sodium sulphate and acetic acid, followed by ODS cartridge clean-up. The developed method was validated for 82 veterinary drugs in bovine muscle and milk at spike levels of 0.01 and 0.1 mg kg - 1 . With the exception of cefoperazone and phenoxymethylpenicillin, all these compounds exhibited sufficient signal intensity at 0.01 μg ml -1 (equivalent to 0.01 mg kg - 1 ), indicating the high sensitivity of the developed method. For most targets, the determined accuracies were within 70-120%, with repeatability and reproducibility being below 20% at both levels. Except for sulfathiazole in bovine muscle, no interfering peaks at target compound retention times were detected in the blank extract, indicating that the developed method is highly selective. The absence of sulfathiazole in bovine muscle was confirmed by simultaneous acquisition at low and high collision energies to afford exact masses of molecular adduct and fragment ions. Satisfactory linearity was observed for all compounds, with matrix effects being negligible for most targets in bovine muscle and milk at both spike levels. Overall, the results suggest that the developed LC-QTOF-MS method is suitable for routine regulatory-purpose analysis of veterinary drugs in bovine muscle and milk.

  14. Identification of skeletal muscle mass depletion across age and BMI groups in health and disease--there is need for a unified definition.

    Science.gov (United States)

    Bosy-Westphal, A; Müller, M J

    2015-03-01

    Although reduced skeletal muscle mass is a major predictor of impaired physical function and survival, it remains inconsistently diagnosed to a lack of standardized diagnostic approaches that is reflected by the variable combination of body composition indices and cutoffs. In this review, we summarized basic determinants of a normal lean mass (age, gender, fat mass, body region) and demonstrate limitations of different lean mass parameters as indices for skeletal muscle mass. A unique definition of lean mass depletion should be based on an indirect or direct measure of skeletal muscle mass normalized for height (fat-free mass index (FFMI), appendicular or lumbal skeletal muscle index (SMI)) in combination with fat mass. Age-specific reference values for FFMI or SMI are more advantageous because defining lean mass depletion on the basis of total FFMI or appendicular SMI could be misleading in the case of advanced age due to an increased contribution of connective tissue to lean mass. Mathematical modeling of a normal lean mass based on age, gender, fat mass, ethnicity and height can be used in the absence of risk-defined cutoffs to identify skeletal muscle mass depletion. This definition can be applied to identify different clinical phenotypes like sarcopenia, sarcopenic obesity or cachexia.

  15. Effect of Body Mass Index on Postural Balance and Muscle Strength in Children Aged 8-10 years

    Directory of Open Access Journals (Sweden)

    Lucky Prasetiowati

    2017-04-01

    Full Text Available Background:Childhood overweight and obesity, which are considered as global epidemic, can be assessed using Body Mass Index (BMI. BMI difference can lead to anatomic changes due to an increased body load. This increase might also affect motor performance, including changes in postural balance and muscle strength. Aims and Objectives: to explain the influence of BMI on postural balance and lower limb muscle strength and to assess the correlation between those two variables in children aged 8-10 years. Material and methods:The sample consisted of 63 children aged 8-10 years, which were divided in 3 groups: BMI-normal, BMI-overweight, and BMI-obese. The postural balance was assessed using single leg balance test on MatScan and the Center Of Pressure (COP area was recorded. Isometric muscle strength of hip extensor and knee extensor were measured using a hand-held dynamometer. Results: Obese children had significantly largerCOP area than overweight (p = 0.004 and normal weight children (p = 0.000.There were no significant differences in hip extensor muscle strength between obese children with overweight and normal weight children (p=0.527. The absolute knee extensor muscle strength in obese group was significantly higher than the overweight and normal group (p = 0.003. However the relative muscle strength of lower limb for obese children was significantly lower than for normal weight. There was no significant correlation between absolute hip extensor and knee extensor muscles strength with COP area. Conclusion: Obese children have decreased postural balance and increased absolute knee extensormuscle strength significantly when compared to overweight and normal children. There is no significant correlation between postural balance and muscle strength.

  16. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability.

    Science.gov (United States)

    Janssen, Ian; Heymsfield, Steven B; Ross, Robert

    2002-05-01

    To establish the prevalence of sarcopenia in older Americans and to test the hypothesis that sarcopenia is related to functional impairment and physical disability in older persons. Cross-sectional survey. Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III). Fourteen thousand eight hundred eighteen adult NHANES III participants aged 18 and older. The presence of sarcopenia and the relationship between sarcopenia and functional impairment and disability were examined in 4,504 adults aged 60 and older. Skeletal muscle mass was estimated from bioimpedance analysis measurements and expressed as skeletal muscle mass index (SMI = skeletal muscle mass/body mass x 100). Subjects were considered to have a normal SMI if their SMI was greater than -one standard deviation above the sex-specific mean for young adults (aged 18-39). Class I sarcopenia was considered present in subjects whose SMI was within -one to -two standard deviations of young adult values, and class II sarcopenia was present in subjects whose SMI was below -two standard deviations of young adult values. The prevalence of class I and class II sarcopenia increased from the third to sixth decades but remained relatively constant thereafter. The prevalence of class I (59% vs 45%) and class II (10% vs 7%) sarcopenia was greater in the older (> or = 60 years) women than in the older men (P normal SMI, respectively. Some of the associations between class II sarcopenia and functional impairment remained significant after adjustment for age, race, body mass index, health behaviors, and comorbidity. Reduced relative skeletal muscle mass in older Americans is a common occurrence that is significantly and independently associated with functional impairment and disability, particularly in older women. These observations provide strong support for the prevailing view that sarcopenia may be an important and potentially reversible cause of

  17. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

    DEFF Research Database (Denmark)

    Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D

    2011-01-01

    Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout...... mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species......, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle....

  18. Genetically Determined Insulin Resistance is Characterized by Down-Regulation of Mitochondrial Oxidative Metabolism in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas M; Skov, Vibe; Wojtaszewski, Jørgen

    2010-01-01

    Transcriptional profiling of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated a co-ordinated down-regulation of oxidative phosphorylation (OxPhos) genes, suggesting a link between insulin resistance and mitochondrial dysfunction. However, whether...... mitochondrial dysfunction is a cause or consequence of insulin resistance remains to be clarified. In the present study, we tested the hypothesis that mitochondrial oxidative metabolism was down-regulated in skeletal muscle of patients with genetically determined insulin resistance. Skeletal muscle biopsies.......02), and complex V (ATP5B; p=0.005). Our data demonstrate that genetically determined insulin resistance is associated with a co-ordinated down-regulation of OxPhos components both at the transcriptional and translational level. These findings suggest that an impaired biological response to insulin in skeletal...

  19. Effect of restriction vegan diet's on muscle mass, oxidative status, and myocytes differentiation: A pilot study.

    Science.gov (United States)

    Vanacore, Daniela; Messina, Giovanni; Lama, Stefania; Bitti, Giuseppe; Ambrosio, Pasqualina; Tenore, Giancarlo; Messina, Antonietta; Monda, Vincenzo; Zappavigna, Silvia; Boccellino, Mariarosaria; Novellino, Ettore; Monda, Marcellino; Stiuso, Paola

    2018-01-10

    This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters, and serum oxidative status. We enrolled three groups of healthy men (omnivores, vegetarians, and vegans) with similar age, weight and BMI, and we observed a significant decrease in muscle mass index and lean body mass in vegan compared to vegetarian and omnivore groups, and higher serum homocysteine levels in vegetarians and vegans compared to omnivores. We studied whether serum from omnivore, vegetarian, and vegan subjects affected oxidative stress, growth and differentiation of both cardiomyoblast cell line H9c2 and H-H9c2 (H9c2 treated with H 2 O 2 to induce oxidative damage). We demonstrated that vegan sera treatment of both H9c2 and H-H9c2 cells induced an increase of TBARS values and cell death and a decrease of free NO 2- compared to vegetarian and omnivorous sera. Afterwards, we investigated the protective effects of vegan, vegetarian, and omnivore sera on the morphological changes induced by H 2 O 2 in H9c2 cell line. We showed that the omnivorous sera had major antioxidant and differentiation properties compared to vegetarian and vegan sera. Finally, we evaluated the influence of the three different groups of sera on MAPKs pathway and our data suggested that ERK expression increased in H-H9c2 cells treated with vegetarian and vegan sera and could promote cell death. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage. © 2018 Wiley Periodicals, Inc.

  20. Predicting skeletal muscle mass from dual-energy X-ray absorptiometry in Japanese prepubertal children.

    Science.gov (United States)

    Midorikawa, T; Ohta, M; Hikihara, Y; Torii, S; Sakamoto, S

    2017-10-01

    We aimed to develop regression-based prediction equations for estimating total and regional skeletal muscle mass (SMM) from measurements of lean soft tissue mass (LSTM) using dual-energy X-ray absorptiometry (DXA) and investigate the validity of these equations. In total, 144 healthy Japanese prepubertal children aged 6-12 years were divided into 2 groups: the model development group (62 boys and 38 girls) and the validation group (26 boys and 18 girls). Contiguous MRI images with a 1-cm slice thickness were obtained from the first cervical vertebra to the ankle joints as reference data. The SMM was calculated from the summation of the digitized cross-sectional areas. Total and regional LSTM was measured using DXA. Strong significant correlations were observed between the site-matched SMM (total, arms, trunk and legs) measured by MRI and the LSTM obtained by DXA in the model development group for both boys and girls (R 2 adj =0.86-0.97, Pprediction equations were applied to the validation group, the measured total (boys 9.47±2.21 kg; girls 8.18±2.62 kg) and regional SMM were very similar to the predicted values for both boys (total SMM 9.40±2.39 kg) and girls (total SMM 8.17±2.57 kg). The results of the Bland-Altman analysis for the validation group did not indicate any bias for either boys or girls with the exception of the arm region for the girls. These results suggest that the DXA-derived prediction equations are precise and accurate for the estimation of total and regional SMM in Japanese prepubertal boys and girls.

  1. Age- and gender-dependent values of skeletal muscle mass in healthy children and adolescents.

    Science.gov (United States)

    Webber, Colin E; Barr, Ronald D

    2012-03-01

    Skeletal muscle mass (SMM) can be extracted from whole-body scans obtained by X-ray-based dual-photon absorptiometry (DXA). There is a need to establish expected age-dependent values for children and adolescents. Appendicular lean tissue mass (ALM) was extracted from whole-body DXA scans in 140 healthy children and adolescents (68 females and 72 males). Whole-body SMM was calculated from ALM using equations developed by Kim et al. (Am J Clin Nutr 84:1014-1020, 2006). Age-dependent patterns of increase in SMM were derived by fitting SMM values to equations that consisted of the sum of two logistic expressions, one accounting for SMM changes during growth and the other for SMM changes during puberty. Normal ranges were defined so that 95% of the SMM values were included. The reproducibility of SMM measurements was obtained from whole-body DXA scans repeated on three occasions in each of a separate group of 32 normal children with repositioning between scans. Normal ranges are presented as equations describing the age-dependent pattern of increase in SMM as well as population standard deviations that increased steadily with age. For 15 children below age 10, SMM reproducibility (95% CI) was 149 g (119-199 g) while for 17 children and adolescents over age 10, reproducibility was 170 g (138-223 g). DXA-based measurements of SMM in children and adolescents are reproducible and can be expressed in terms of age-dependent Z scores.

  2. Pre-hospital dietary intake correlates with muscle mass at the time of fracture in older hip fractured patients

    Directory of Open Access Journals (Sweden)

    Riccardo eCalvani

    2014-11-01

    Full Text Available Background. Failure to meet an adequate dietary intake is involved in the pathogenesis of sarcopenia and osteoporosis, which in turn increase the risk for falls and fractures, respectively. Older people with hip fracture are often protein-malnourished at hospitalization. Whether low protein-energy intake is associated with muscle atrophy in hip fractured patients is presently unknown. This information is necessary for the development of novel strategies to manage this especially vulnerable patient population. The aim of this study was therefore to explore the relationship between dietary intake and muscle mass in older hip fractured patients.Methods. Analyses were conducted in hip fractured elderly admitted to an orthopedic and trauma surgery ward (University Hospital. Muscle mass was estimated by bioelectrical impedance analysis within 24 h from admission. Dietary information was collected via 24-h dietary recall and nutrient intakes calculated by a nutrition software.Results. Among 62 hip fractured patients (mean age 84.6±7.6 years, 84% women, the average energy intake was 929.2±170.3 Kcal/day, with higher values reported by men (1.046.8±231.4 Kcal/day relative to women (906.5±148.3 Kcal/day; p=0.01. Absolute and normalized protein intake was 50.0±13.5 g/day and 0.88±0.27 g/kg (body weight/day, respectively, with no gender differences. A positive correlation was determined between total energy intake and muscle mass (r=0.384; p=0.003. Similarly, protein and leucine consumption was positively correlated with muscle mass (r=0.367 and 0.311, respectively; p=0.005 for both.Conclusions. A low intake of calories, protein and leucine is associated with reduced muscle mass in hip fractured elderly. Given the relevance of sarcopenia as a risk factor for adverse outcomes in this patient population, our findings highlight the importance of a comprehensive dietary assessment for the detection of nutritional deficits predisposing to or aggravating

  3. Skeletal muscle mass and body fat in relation to successful ageing of older adults: The multi-national MEDIS study.

    Science.gov (United States)

    Tyrovolas, Stefanos; Haro, Josep-Maria; Mariolis, Anargiros; Piscopo, Suzanne; Valacchi, Giuseppe; Bountziouka, Vassiliki; Anastasiou, Foteini; Zeimbekis, Akis; Tyrovola, Dimitra; Foscolou, Alexandra; Gotsis, Efthimios; Metallinos, George; Tur, Josep-Antoni; Matalas, Antonia; Lionis, Christos; Polychronopoulos, Evangelos; Panagiotakos, Demosthenes

    2016-01-01

    The determinants that promote successful ageing still remain unknown. The aim of the present work was to evaluate the role of skeletal muscle mass and body fat percentage (BF%), in the level of successful ageing. during 2005-2011, 2663 older (aged 65-100 years) from 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the study. Appendicular skeletal muscle mass (ASM), skeletal muscle mass index (SMI) and BF% were calculated using population formulas. Dietary habits, energy intake, expenditure and energy balance were derived throughout standard procedures. A successful ageing index ranging from 0 to 10 was used. The mean ASM mass was 24±6.0kg, the SMI was 0.84±0.21 and the BF% was 44%. Females had lower SMI and higher BF% in comparison with males, respectively [(SMI: 0.66±0.09 vs. 1.03±0.11; BF%: 51% vs. 34%, (pageing, while changes in BF% [b-coefficient (95% CI): -0.04 (-0.05 to -0.03)] were inversely associated with successful ageing. Results from sensitivity analysis showed that the effects of variations on body composition were consistent, less pronounced in the positive energy balance group and more pronounced among the oldest old. Body composition changes seem to be associated with lower quality of life in the older adults, as measured through successful ageing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Metabolic reprogramming as a novel regulator of skeletal muscle development and regeneration.

    Science.gov (United States)

    Ryall, James G

    2013-09-01

    Adult skeletal muscle contains a resident population of stem cells, termed satellite cells, that exist in a quiescent state. In response to an activating signal (such as physical trauma), satellite cells enter the cell cycle and undergo multiple rounds of proliferation, followed by differentiation, fusion, and maturation. Over the last 10-15 years, our understanding of the transcriptional regulation of this stem cell population has greatly expanded, but there remains a dearth of knowledge with regard to the initiating signal leading to these changes in transcription. The recent renewed interest in the metabolic regulation of both cancer and stem cells, combined with previous findings indicating that satellite cells preferentially colocalize with blood vessels, suggests that satellite cell function may be regulated by changes in cellular metabolism. This review aims to describe what is currently known about satellite cell metabolism during changes in cell fate, as well as to describe some of the exciting findings in other cell types and how these might relate to satellite cells. © 2013 The Author Journal compilation © 2013 FEBS.

  5. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to casein protein hydrolysates and growth or maintenance of muscle mass (ID 1498), increase in endurance performance (ID 660, 1497) and faster recovery from muscle

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to casein protein hydrolysates and growth or maintenance of muscle mass, increase in endurance performance and faster recovery from muscle fatigue after exercise. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article...

  6. High insulin-like growth factor-binding protein-1 (IGFBP-1) is associated with low relative muscle mass in older women

    DEFF Research Database (Denmark)

    Stilling, Frej; Wallenius, Sara; Michaëlsson, Karl

    2017-01-01

    . In the present study we investigate the association between serum IGFBP-1 and muscle mass. Design Cross-sectional analysis of 4908 women, between 55 and 85 years old, participating in the Swedish Mammography Cohort-Clinical. Methods We defined low relative muscle mass (LRMM) as an appendicular lean mass divided...... relative muscle mass. High IGFBP-1 may be a marker of a catabolic state.......Objective Skeletal muscles serve several important roles in maintaining good health. Insulin-like growth factor-1 (IGF-1) is a promoter of protein synthesis in skeletal muscle. Its binding protein, Insulin-like growth factor-binding protein-1 (IGFBP-1) can be one determinant of IGF-1 activity...

  7. The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+ mouse.

    Directory of Open Access Journals (Sweden)

    James P White

    Full Text Available Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+ mouse is not known. Cachexia progression was studied in Apc(Min/+ mice that were either weight stable (WS or had initial (≤5%, intermediate (6-19%, or extreme (≥20% body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172, AMPK activity, and raptor phosphorylation (Ser 792 were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

  8. The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse

    Science.gov (United States)

    White, James P.; Baynes, John W.; Welle, Stephen L.; Kostek, Matthew C.; Matesic, Lydia E.; Sato, Shuichi; Carson, James A.

    2011-01-01

    Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The ApcMin/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the ApcMin/+ mouse is not known. Cachexia progression was studied in ApcMin/+ mice that were either weight stable (WS) or had initial (≤5%), intermediate (6–19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process. PMID:21949739

  9. MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

    Science.gov (United States)

    Shi, Lei; Zhou, Bo; Li, Pinghua; Schinckel, Allan P; Liang, Tingting; Wang, Han; Li, Huizhi; Fu, Lingling; Chu, Qingpo; Huang, Ruihua

    2015-09-01

    MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development. In a previous study we observed that miR-128 was highly expressed in skeletal muscle. However, its function in regulating skeletal muscle development is not clear. Our hypothesis was that miR-128 is involved in the regulation of the proliferation and differentiation of skeletal myoblasts. In this study, through bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding domain sequence (CDS) region, resulting in down-regulating of myostatin post-transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12 myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had completely opposite effects. In addition, ectopic miR-128 regulated the expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and 7. Furthermore, an inverse relationship was found between the expression of miR-128 and MSTN protein expression in vivo and in vitro. Taken together, these results reveal that there is a novel pathway in skeletal muscle development in which miR-128 regulates myostatin at CDS region to inhibit proliferation but promote differentiation of myoblast cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Guanine nucleotide regulation of α1-adrenergic receptors of muscle and kidney eptihelial cells

    International Nuclear Information System (INIS)

    Terman, B.I.; Hughes, R.J.; Slivka, S.R.; Insel, P.A.

    1986-01-01

    The authors have examined the effect of guanine nucleotides on the interaction of adrenergic agents with α 1 -adrenergic receptors of two cell lines, the Madin-Darby Canine Kidney (MDCK) and BC3H-1 muscle cells. While gaunylylimidodiphosphoate (Gpp(NH)p) had no effect on the affinity or the total number of [ -3 H]prazosin binding sites in membranes prepared from these cells, the nucleotide decreased the apparent affinity of the agonist epinephrine in competing for [ 3 H]prazosin binding sites in both cell types. The EC 50 of Gpp(NH)p was ∼100 μM, and a maximal effect was seen at 500 μM. In contrast, 100 μM Gpp(NH)p yielding maximal shifts in binding of epinephrine to β-adrenergic receptors in BC3H-1 cell membranes. Guanine nucleotides were significantly more effective than adenine nucleotides in shifting agonist affinity for the α 1 -receptor and Mg ++ was required to observe a maximal effect. α 1 -receptor agonists activated phosphatidylinositol (PI) hydrolysis in both cell types, but have no direct effect on membrane adenylate cyclase activity. In intact BC3H-1 cells, α 1 -agonists inhibited β-adrenergic cAMP production, an effect which appears in preliminary studies not to result from enhanced phosphodieterase activity. These results show that agonist binding to α 1 -adrenergic receptors in mammalian kidney and muscle cells is regulated by guanine nucleotides. This regulation and inturn transmembrane signalling (PI hydrolysis) by these receptors appear to involve a guanine nucleotide binding (G) protein, which may be different than G/sub s/ and G/sub i/

  11. Regulation of CCL5 expression in smooth muscle cells following arterial injury.

    Directory of Open Access Journals (Sweden)

    Huan Liu

    Full Text Available Chemokines play a crucial role in inflammation and in the pathophysiology of atherosclerosis by recruiting inflammatory immune cells to the endothelium. Chemokine CCL5 has been shown to be involved in atherosclerosis progression. However, little is known about how CCL5 is regulated in vascular smooth muscle cells. In this study we report that CCL5 mRNA expression was induced and peaked in aorta at day 7 and then declined after balloon artery injury, whereas IP-10 and MCP-1 mRNA expression were induced and peaked at day 3 and then rapidly declined.The expression of CCL5 receptors (CCR1, 3 & 5 were also rapidly induced and then declined except CCR5 which expression was still relatively high at day 14 after balloon injury. In rat smooth muscle cells (SMCs, similar as in aorta CCL5 mRNA expression was induced and kept increasing after LPS plus IFN-gamma stimulation, whereas IP-10 mRNA expression was rapidly induced and then declined. Our data further indicate that induction of CCL5 expression in SMCs was mediated by IRF-1 via binding to the IRF-1 response element in CCL5 promoter. Moreover, p38 MAPK was involved in suppression of CCL5 and IP-10 expression in SMCs through common upstream molecule MKK3. The downstream molecule MK2 was required for p38-mediated CCL5 but not IP-10 inhibition. Our findings indicate that CCL5 induction in aorta and SMCs is mediated by IRF-1 while activation of p38 MAPK signaling inhibits CCL5 and IP-10 expression. Methods targeting MK2 expression could be used to selectively regulate CCL5 but not IP-10 expression in SMCs.

  12. Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

    NARCIS (Netherlands)

    de Theije, Chiel C.; Langen, Ramon C. J.; Lamers, Wouter H.; Schols, Annemie M. W. J.; Köhler, S. Eleonore

    2013-01-01

    The balance of muscle protein synthesis and degradation determines skeletal muscle mass. We hypothesized that hypoxia-induced muscle atrophy and alterations in the regulation of muscle protein turnover include a hypoxia-specific component, in addition to the observed effects of reduction in food

  13. Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

    International Nuclear Information System (INIS)

    Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia; Mazzanti, Benedetta; Quercioli, Franco; Zecchi-Orlandini, Sandra; Formigli, Lucia

    2014-01-01

    Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7 + satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration

  14. Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Mazzanti, Benedetta [Dept. of Experimental and Clinical Medicine—Section of Haematology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Quercioli, Franco [CNR-National Institute of Optics (INO), Largo Enrico Fermi 6, 50125 Arcetri-Florence (Italy); Zecchi-Orlandini, Sandra [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Formigli, Lucia, E-mail: formigli@unifi.it [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy)

    2014-05-01

    Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7{sup +} satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.

  15. Slow movement resistance training using body weight improves muscle mass in the elderly: A randomized controlled trial.

    Science.gov (United States)

    Tsuzuku, S; Kajioka, T; Sakakibara, H; Shimaoka, K

    2018-04-01

    To examine the effect of a 12-week slow movement resistance training using body weight as a load (SRT-BW) on muscle mass, strength, and fat distribution in healthy elderly people. Fifty-three men and 35 women aged 70 years old or older without experience in resistance training participated, and they were randomly assigned to a SRT-BW group or control group. The control group did not receive any intervention, but participants in this group underwent a repeat measurement 12 weeks later. The SRT-BW program consisted of 3 different exercises (squat, tabletop push-up, and sit-up), which were designed to stimulate anterior major muscles. Initially, these exercises were performed by 2 sets of 10 repetitions, and subsequently, the number of repetitions was increased progressively by 2 repetitions every 4 weeks. Participants were instructed to perform each eccentric and concentric phase of movement slowly (spending 4 seconds on each movement), covering the full range of motion. We evaluated muscle mass, strength, and fat distribution at baseline and after 12 weeks of training. Changes over 12 weeks were significantly greater in the SRT-BW group than in the control group, with a decrease in waist circumference, hip circumference, and abdominal preperitoneal and subcutaneous fat thickness, and an increase in thigh muscle thickness, knee extension strength, and hip flexion strength. In conclusion, relatively short-term SRT-BW was effective in improving muscle mass, strength, and fat distribution in healthy elderly people. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. The Influence of Body Mass Index, Sex, & Muscle Activation on Pressure Distribution During Lateral Falls on the Hip.

    Science.gov (United States)

    Pretty, Steven P; Martel, Daniel R; Laing, Andrew C

    2017-12-01

    Hip fracture incidence rates are influenced by body mass index (BMI) and sex, likely through mechanistic pathways that influence dynamics of the pelvis-femur system during fall-related impacts. The goal of this study was to extend our understanding of these impact dynamics by investigating the effects of BMI, sex, and local muscle activation on pressure distribution over the hip region during lateral impacts. Twenty participants underwent "pelvis-release experiments" (which simulate a lateral fall onto the hip), including muscle-'relaxed' and 'contracted' trials. Males and low-BMI individuals exhibited 44 and 55% greater peak pressure, as well as 66 and 56% lower peripheral hip force, compared to females and high-BMI individuals, respectively. Local muscle activation increased peak force by 10%, contact area by 17%, and peripheral hip force by 11% compared to relaxed trials. In summary, males and low-BMI individuals exhibited more concentrated loading over the greater trochanter. Muscle activation increased peak force, but this force was distributed over a larger area, preventing increased localized loading over the greater trochanter. These findings suggest potential value in incorporating sex, gender, and muscle activation-specific force distributions as inputs into computational tissue-level models, and have implications for the design of personalized protective devices including wearable hip protectors.

  17. REGULATION OF AUTOPHAGY AND THE UBIQUITIN-€“ PROTEASOME SYSTEM BY THE FoxO TRANSCRIPTIONAL NETWORK DURING MUSCLE ATROPHY

    OpenAIRE

    PESCATORE, FRANCESCA

    2016-01-01

    Skeletal muscle can adapt its mass in response to physical activity, metabolism and hormones. The control of muscle size depends on the coordinated balance between protein synthesis and protein degradation. Mechanical overload or anabolic hormonal stimulation shifts the balance towards protein synthesis leading to an increase in fiber size, a process called hypertrophy. Conversely, in catabolic conditions protein degradation exceeds protein synthesis resulting into muscle weakness and muscle ...

  18. Vitamin D and muscle trophicity.

    Science.gov (United States)

    Domingues-Faria, Carla; Boirie, Yves; Walrand, Stéphane

    2017-05-01

    We review recent findings on the involvement of vitamin D in skeletal muscle trophicity. Vitamin D deficiencies are associated with reduced muscle mass and strength, and its supplementation seems effective to improve these parameters in vitamin D-deficient study participants. Latest investigations have also evidenced that vitamin D is essential in muscle development and repair. In particular, it modulates skeletal muscle cell proliferation and differentiation. However, discrepancies still exist about an enhancement or a decrease of muscle proliferation and differentiation by the vitamin D. Recently, it has been demonstrated that vitamin D influences skeletal muscle cell metabolism as it seems to regulate protein synthesis and mitochondrial function. Finally, apart from its genomic and nongenomic effects, recent investigations have demonstrated a genetic contribution of vitamin D to muscle functioning. Recent studies support the importance of vitamin D in muscle health, and the impact of its deficiency in regard to muscle mass and function. These 'trophic' properties are of particular importance for some specific populations such as elderly persons and athletes, and in situations of loss of muscle mass or function, particularly in the context of chronic diseases.

  19. Propeptide-mediated inhibition of myostatin increases muscle mass through inhibiting proteolytic pathways in aged mice.

    Science.gov (United States)

    Collins-Hooper, Henry; Sartori, Roberta; Macharia, Raymond; Visanuvimol, Korntip; Foster, Keith; Matsakas, Antonios; Flasskamp, Hannah; Ray, Steve; Dash, Philip R; Sandri, Marco; Patel, Ketan

    2014-09-01

    Mammalian aging is accompanied by a progressive loss of skeletal muscle, a process called sarcopenia. Myostatin, a secreted member of the transforming growth factor-β family of signaling molecules, has been shown to be a potent inhibitor of muscle growth. Here, we examined whether muscle growth could be promoted in aged animals by antagonizing the activity of myostatin through the neutralizing activity of the myostatin propeptide. We show that a single injection of an AAV8 virus expressing the myostatin propeptide induced an increase in whole body weights and all muscles examined within 7 weeks of treatment. Our cellular studies demonstrate that muscle enlargement was due to selective fiber type hypertrophy, which was accompanied by a shift toward a glycolytic phenotype. Our molecular investigations elucidate the mechanism underpinning muscle hypertrophy by showing a decrease in the expression of key genes that control ubiquitin-mediated protein breakdown. Most importantly, we show that the hypertrophic muscle that develops as a consequence of myostatin propeptide in aged mice has normal contractile properties. We suggest that attenuating myostatin signaling could be a very attractive strategy to halt and possibly reverse age-related muscle loss. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Influence of step-height and body mass on gastrocnemius muscle fascicle behavior during stair ascent.

    NARCIS (Netherlands)

    Spanjaard, M.; Reeves, N.D.; van Dieen, J.H.; Baltzopoulos, V.; Maganaris, C.N.

    2008-01-01

    To better understand the role of the ankle plantar flexor muscles in stair negotiation, we examined the effects of manipulation of kinematic and kinetic constraints on the behavior of the gastrocnemius medialis (GM) muscle during stair ascent. Ten subjects ascended a four-step staircase at four

  1. The Ror1 receptor tyrosine kinase plays a critical role in regulating satellite cell proliferation during regeneration of injured muscle.

    Science.gov (United States)

    Kamizaki, Koki; Doi, Ryosuke; Hayashi, Makoto; Saji, Takeshi; Kanagawa, Motoi; Toda, Tatsushi; Fukada, So-Ichiro; Ho, Hsin-Yi Henry; Greenberg, Michael Eldon; Endo, Mitsuharu; Minami, Yasuhiro

    2017-09-22

    The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles. Importantly, expression of Ror1 , but not Ror2 , was induced primarily in Pax7-positive satellite cells (SCs) after muscle injury, and administration of neutralizing antibodies decreased the proportion of Pax7-positive proliferative SCs after muscle injury. We also found that stimulation of a mouse myogenic cell line, C2C12 cells, with TNF-α or IL-1β induced expression of Ror1 via NF-κB activation and that suppressed expression of Ror1 inhibited their proliferative responses in SCs. Intriguingly, SC-specific depletion of Ror1 decreased the number of Pax7-positive SCs after muscle injury. Collectively, these findings indicate for the first time that Ror1 has a critical role in regulating SC proliferation during skeletal muscle regeneration. We conclude that Ror1 might be a suitable target in the development of diagnostic and therapeutic approaches to manage muscular disorders. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men.

    Directory of Open Access Journals (Sweden)

    Hélène De Naeyer

    Full Text Available OBJECTIVE: The relationship between serum testosterone (T levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings. DESIGN: 677 men (25-45 years were recruited in a cross-sectional, population-based sibling pair study. METHODS: Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs, sex steroid levels (by LC-MS/MS, body composition (by DXA, muscle cross-sectional area (CSA (by pQCT, muscle force (isokinetic peak torque, grip strength and anthropometrics were studied using linear mixed-effect modelling. RESULTS: Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT and free T (FT levels were positively related to muscle CSA, whereas estradiol (E2 and free E2 (FE2 concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats. CONCLUSIONS: Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR

  3. Effects of high-intensity exercise and protein supplement on muscle mass in ADL dependent older people with and without malnutrition: a randomized controlled trial.

    Science.gov (United States)

    Carlsson, M; Littbrand, H; Gustafson, Y; Lundin-Olsson, L; Lindelöf, N; Rosendahl, E; Håglin, L

    2011-08-01

    Loss of muscle mass is common among old people living in institutions but trials that evaluate interventions aimed at increasing the muscle mass are lacking. Objective, participants and intervention: This randomized controlled trial was performed to evaluate the effect of a high-intensity functional exercise program and a timed protein-enriched drink on muscle mass in 177 people aged 65 to 99 with severe physical or cognitive impairments, and living in residential care facilities. Three-month high-intensity exercise was compared with a control activity and a protein-enriched drink was compared with a placebo drink. A bioelectrical impedance spectrometer (BIS) was used in the evaluation. The amount of muscle mass and body weight (BW) were followed-up at three and six months and analyzed in a 2 x 2 factorial ANCOVA, using the intention to treat principle, and controlling for baseline values. At 3-month follow-up there were no differences in muscle mass and BW between the exercise and the control group or between the protein and the placebo group. No interaction effects were seen between the exercise and nutritional intervention. Long-term negative effects on muscle mass and BW was seen in the exercise group at the 6-month follow-up. A three month high-intensity functional exercise program did not increase the amount of muscle mass and an intake of a protein-enriched drink immediately after the exercise did not induce any additional effect on muscle mass. There were negative long-term effects on muscle mass and BW, indicating that it is probably necessary to compensate for an increased energy demand when offering a high-intensity exercise program.

  4. Increase in relative skeletal muscle mass over time and its inverse association with metabolic syndrome development: a 7-year retrospective cohort study.

    Science.gov (United States)

    Kim, Gyuri; Lee, Seung-Eun; Jun, Ji Eun; Lee, You-Bin; Ahn, Jiyeon; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Jee, Jae Hwan; Lee, Moon-Kyu; Kim, Jae Hyeon

    2018-02-05

    Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54-0.68). Furthermore, compared with SMI changes metabolic syndrome development were 0.87 (95% CI 0.78-0.97) for 0-1% changes and 0.67 (0.56-0.79) for > 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.

  5. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

    International Nuclear Information System (INIS)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S.; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-01-01

    The voltage-gated calcium channel (Ca v ) β 1a subunit (Ca v β 1a ) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca v β 1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca v β 1a NH 2 -terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca v β 1a /YFP shows that TnT3 facilitates Ca v β 1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca v β 1a is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca v β 1a . • We mapped TnT3 and Ca v β 1a interaction domain. • TnT3 facilitates Ca v β 1a nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation

  6. LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration

    Science.gov (United States)

    Wang, Lijun; Zhao, Yu; Bao, Xichen; Zhu, Xihua; Kwok, Yvonne Ka-yin; Sun, Kun; Chen, Xiaona; Huang, Yongheng; Jauch, Ralf; Esteban, Miguel A; Sun, Hao; Wang, Huating

    2015-01-01

    Emerging studies document the roles of long non-coding RNAs (LncRNAs) in regulating gene expression at chromatin level but relatively less is known how they regulate DNA methylation. Here we identify an lncRNA, Dum (developmental pluripotency-associated 2 (Dppa2) Upstream binding Muscle lncRNA) in skeletal myoblast cells. The expression of Dum is dynamically regulated during myogenesis in vitro and in vivo. It is also transcriptionally induced by MyoD binding upon myoblast differentiation. Functional analyses show that it promotes myoblast differentiation and damage-induced muscle regeneration. Mechanistically, Dum was found to silence its neighboring gene, Dppa2, in cis through recruiting Dnmt1, Dnmt3a and Dnmt3b. Furthermore, intrachromosomal looping between Dum locus and Dppa2 promoter is necessary for Dum/Dppa2 interaction. Collectively, we have identified a novel lncRNA that interacts with Dnmts to regulate myogenesis. PMID:25686699

  7. Clinical effectiveness of protein and amino acid supplementation on building muscle mass in elderly people: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhe-rong Xu

    Full Text Available A major reason for the loss of mobility in elderly people is the gradual loss of lean body mass known as sarcopenia. Sarcopenia is associated with a lower quality of life and higher healthcare costs. The benefit of strategies that include nutritional intervention, timing of intervention, and physical exercise to improve muscle loss unclear as finding from studies investigating this issue have been inconsistent. We have performed a systematic review and meta-analysis to assess the ability of protein or amino acid supplementation to augment lean body mass or strength of leg muscles in elderly patients.Nine studies met the inclusion criteria of being a prospective comparative study or randomized controlled trial (RCT that compared the efficacy of an amino acid or protein supplement intervention with that of a placebo in elderly people (≥ 65 years for the improvement of lean body mass (LBM, leg muscle strength or reduction associated with sarcopenia.The overall difference in mean change from baseline to the end of study in LBM between the treatment and placebo groups was 0.34 kg which was not significant (P = 0.386. The overall differences in mean change from baseline in double leg press and leg extension were 2.14 kg (P = 0.748 and 2.28 kg (P = 0.265, respectively, between the treatment group and the placebo group.These results indicate that amino acid/protein supplements did not increase lean body mass gain and muscle strength significantly more than placebo in a diverse elderly population.

  8. Effect of strength training and short-term detraining on muscle mass in women aged over 50 years old

    Directory of Open Access Journals (Sweden)

    Maryam Delshad

    2013-01-01

    Full Text Available Background: The loss of muscle mass is associated with aging. The aim of this study was to determine the effects of resistance training and detraining on muscle mass in elderly women. Methods: Twenty post-menopausal women aged ≥50 years old were enrolled. Matching for age, they were randomly assigned into control and resistance training group (RT. The intervention consisted of three sets of 10 repetitions for 10 movements with Thera-Band tubing (based on 80-100% 10-RM, three times a week, for 12 weeks and thereafter, four weeks detraining. Skinfold thickness was determined by caliper. Percentage of body fat was estimated from skinfold thickness (triceps and subscapular by McArdle method. Fat mass (FM and fat-free mass (FFM were calculated. Range of motion for trunk flexion and extension was determined. Results: During 12 weeks of intervention, significant increases were observed in 1-RM of biceps curl, FFM, trunk flexion and extension and significant decreases during four weeks detraining in RT group. The RT group demonstrated significant decreases during resistance training and increases during detraining in skinfold thickness. FFM, trunk flexion, and extension decreased and skinfold thickness, %FM, and weight of body fat increased in the control group (P < 0.05. Conclusions: Resistance training with Thera-Band enhanced strength and muscle endurance in elderly women and a 4-week detraining period had an adverse effect on muscle power. This suggests that a strength training program is an effective intervention to prevent functional reductions, and can contribute to improve neuromuscular function in older adults.

  9. Muscle mass and physical recovery in ICU: innovations for targeting of nutrition and exercise.

    Science.gov (United States)

    Wischmeyer, Paul E; Puthucheary, Zudin; San Millán, Iñigo; Butz, Daniel; Grocott, Michael P W

    2017-08-01

    We have significantly improved hospital mortality from sepsis and critical illness in last 10 years; however, over this same period we have tripled the number of 'ICU survivors' going to rehabilitation. Furthermore, as up to half the deaths in the first year following ICU admission occur post-ICU discharge, it is unclear how many of these patients ever returned home or a meaningful quality of life. For those who do survive, recent data reveals many 'ICU survivors' will suffer significant functional impairment or post-ICU syndrome (PICS). Thus, new innovative metabolic and exercise interventions to address PICS are urgently needed. These should focus on optimal nutrition and lean body mass (LBM) assessment, targeted nutrition delivery, anabolic/anticatabolic strategies, and utilization of personalized exercise intervention techniques, such as utilized by elite athletes to optimize preparation and recovery from critical care. New data for novel LBM analysis technique such as computerized tomography scan and ultrasound analysis of LBM are available showing objective measures of LBM now becoming more practical for predicting metabolic reserve and effectiveness of nutrition/exercise interventions. 13C-Breath testing is a novel technique under study to predict infection earlier and predict over-feeding and under-feeding to target nutrition delivery. New technologies utilized routinely by athletes such as muscle glycogen ultrasound also show promise. Finally, the role of personalized cardiopulmonary exercise testing to target preoperative exercise optimization and post-ICU recovery are becoming reality. New innovative techniques are demonstrating promise to target recovery from PICS utilizing a combination of objective LBM and metabolic assessment, targeted nutrition interventions, personalized exercise interventions for prehabilitation and post-ICU recovery. These interventions should provide hope that we will soon begin to create more 'survivors' and fewer victim's post

  10. Expression of muscle anabolic and metabolic factors in mechanically loaded MLO-Y4 osteocytes

    NARCIS (Netherlands)

    Juffer, P.; Jaspers, R.T.; Lips, P.; Bakker, A.D.; Klein-Nulend, J.

    2012-01-01

    Lack of physical activity results in muscle atrophy and bone loss, which can be counteracted by mechanical loading. Similar molecular signaling pathways are involved in the adaptation of muscle and bone mass to mechanical loading. Whether anabolic and metabolic factors regulating muscle mass, i.e.,

  11. Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men.

    Science.gov (United States)

    Nedergaard, Anders; Sun, Shu; Karsdal, Morten A; Henriksen, Kim; Kjær, Michael; Lou, Yunyun; He, Yi; Zheng, Qinlong; Suetta, Charlotte

    2013-12-01

    Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflected by peptide biomarkers derived from type VI collagen processing released in the circulation. In order to test this hypothesis, we set out to develop an ELISA assay against an type VI collagen N-terminal globular domain epitope (IC6) and measured the levels of IC6 and an MMP-generated degradation fragment of collagen 6, (C6M) in a human immobilization-remobilization study setup with young (n = 11) and old (n = 9) men. They were subjected to 2 weeks of unilateral lower limb immobilization followed by 4 weeks of remobilization including thrice weekly resistance training, using the contralateral leg as internal controls. Subjects were sampled for strength, quadriceps muscle volume and blood at baseline (PRE), post-immobilization (2W), and post-remobilization (4W). Blood were subsequently analyzed for levels of the C6M and IC6 biomarkers. We subsequently tested if there was any correlation between C6M, IC6, or the C6M/IC6 ratio and muscle mass or strength at baseline. We also tested whether there was any relation between these biomarkers and changes in muscle mass or strength with immobilization or remobilization. The model produced significant loss of muscle mass and strength in the immobilized leg. This loss was bigger in young subjects than in elderly, but whereas the young recovered almost fully, the elderly had limited regrowth of muscle. We found a significant correlation between IC6 and muscle mass at baseline in young subjects (R (2) = 0.6563, p = 0.0045), but none in the elderly. We also found a significant correlation between C6M measured at the 4W time point and the change in muscle mass during remobilization, again only manifesting in the young

  12. Lean body mass and muscle function in head and neck cancer patients and healthy individuals - results from the DAHANCA 25 study

    DEFF Research Database (Denmark)

    Lønbro, Simon; Dalgas, Ulrik; Primdahl, Hanne

    2013-01-01

    Abstract Introduction. Loss of lean body mass is common following radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) and may reduce maximal muscle strength and functional performance. However, the associations between lean body mass, muscle strength and functional...... m max gait speed, 30 s chair rise, 30 s arm curl, stair climb) from HNSCC patients from the DAHANCA 25 trials and data from 24 healthy individuals were included. Results. Lean body mass and maximal muscle strength were significantly associated according to the gender and age-adjusted linear...... regression model (p regression analyses showed that HNSCC patients expressed significant lower levels of the investigated variables after radiotherapy...

  13. Oxygen-coupled Redox Regulation of the Skeletal Muscle Ryanodine Receptor/Ca2+ Release Channel (RyR1)

    Science.gov (United States)

    Sun, Qi-An; Wang, Benlian; Miyagi, Masaru; Hess, Douglas T.; Stamler, Jonathan S.

    2013-01-01

    In mammalian skeletal muscle, Ca2+ release from the sarcoplasmic reticulum (SR) through the ryanodine receptor/Ca2+-release channel RyR1 can be enhanced by S-oxidation or S-nitrosylation of separate Cys residues, which are allosterically linked. S-Oxidation of RyR1 is coupled to muscle oxygen tension (pO2) through O2-dependent production of hydrogen peroxide by SR-resident NADPH oxidase 4. In isolated SR (SR vesicles), an average of six to eight Cys thiols/RyR1 monomer are reversibly oxidized at high (21% O2) versus low pO2 (1% O2), but their identity among the 100 Cys residues/RyR1 monomer is unknown. Here we use isotope-coded affinity tag labeling and mass spectrometry (yielding 93% coverage of RyR1 Cys residues) to identify 13 Cys residues subject to pO2-coupled S-oxidation in SR vesicles. Eight additional Cys residues are oxidized at high versus low pO2 only when NADPH levels are supplemented to enhance NADPH oxidase 4 activity. pO2-sensitive Cys residues were largely non-overlapping with those identified previously as hyperreactive by administration of exogenous reagents (three of 21) or as S-nitrosylated. Cys residues subject to pO2-coupled oxidation are distributed widely within the cytoplasmic domain of RyR1 in multiple functional domains implicated in RyR1 activity-regulating interactions with the L-type Ca2+ channel (dihydropyridine receptor) and FK506-binding protein 12 as well as in “hot spot” regions containing sites of mutation implicated in malignant hyperthermia and central core disease. pO2-coupled disulfide formation was identified, whereas neither S-glutathionylated nor sulfenamide-modified Cys residues were observed. Thus, physiological redox regulation of RyR1 by endogenously generated hydrogen peroxide is exerted through dynamic disulfide formation involving multiple Cys residues. PMID:23798702

  14. Sphingosine-1-phosphate regulates RGS2 and RGS16 mRNA expression in vascular smooth muscle cells

    NARCIS (Netherlands)

    Hendriks-Balk, Mariëlle C.; Hajji, Najat; van Loenen, Pieter B.; Michel, Martin C.; Peters, Stephan L. M.; Alewijnse, Astrid E.

    2009-01-01

    Regulator of G protein signalling (RGS) protein expression is altered under growth promoting conditions in vascular smooth muscle cells (VSMCs). Since sphingosine-1-phosphate (S1P) is an important growth stimulatory factor, we investigated whether stimulation of VSMCs with S1P results in alterations

  15. Low birth weight and zygosity status is associated with defective muscle glycogen and glycogen synthase regulation in elderly twins

    DEFF Research Database (Denmark)

    Poulsen, Pernille; Wojtaszewski, Jørgen; Richter, Erik

    2007-01-01

    OBJECTIVE: An adverse intrauterine environment indicated by both low birth weight and monozygosity is associated with an age- or time-dependent reduction in glucose disposal and nonoxidative glucose metabolism in twins, suggesting impaired regulation of muscle glycogen synthesis. RESEARCH DESIGN ...

  16. Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Roepstorff, Carsten; Halberg, Nils; Hillig, Thore

    2005-01-01

    Intracellular mechanisms regulating fat oxidation were investigated in human skeletal muscle during exercise. Eight young, healthy, moderately trained men performed bicycle exercise (60 min, 65% peak O2 consumption) on two occasions, where they ingested either 1) a high-carbohydrate diet (H-CHO) ...

  17. Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2 beta in Developing and Mature Mouse Skeletal Muscle

    NARCIS (Netherlands)

    Kuperman, Yael; Issler, Orna; Vaughan, Joan; Bilezikjian, Louise; Vale, Wylie; Chen, Alon

    Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2

  18. [Molecular mechanisms of skeletal muscle hypertrophy].

    Science.gov (United States)

    Astratenkova, I V; Rogozkin, V A

    2014-06-01

    Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

  19. Down-regulation of endothelin binding sites in rat vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Roubert, P.; Gillard, V.; Plas, P.; Chabrier, P.E.; Braquet, P.

    1990-01-01

    In cultured rat aortic smooth muscle cells, [ 125 I]endothelin (ET-1) bound to an apparent single class of high affinity recognition sites with a dissociation constant of 1.84 +/- 0.29 nmol/L and a maximum binding of 62 +/- 10.5 fmol/10(6) cells. The binding was not affected by calcium antagonists or vasoactive substances, including angiotensin II, arginine vasopressin, atrial natriuretic factor and bradykinin. Exposure of the cells to ET-1 (0.01 nmol/L to 10 nmol/L) resulted in an apparent dose-dependent reduction of the number of endothelin binding sites with no significant modification of its binding affinity. The time course of the down-regulation of ET-1 binding sites showed that this effect was present after 30 min incubation and persisted after 18 h. This indicates that down-regulation of ET-1 binding sites can modulate the activity of ET-1 and suggests a rapid internalization of ET-1 in vascular cells

  20. Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise

    DEFF Research Database (Denmark)

    Kristensen, Dorte Enggaard; Albers, Peter Hjorth; Prats, Clara

    2015-01-01

    are expressed in a fibre type-dependent manner and that fibre type-specific activation of AMPK and downstream targets is dependent on exercise intensity. Pools of type I and II fibres were prepared from biopsies of m. vastus lateralis from healthy men before and after two exercise trials; A) continuous cycling......AMP-activated protein kinase (AMPK) is a regulator of energy homeostasis during exercise. Studies suggest muscle fibre type-specific AMPK expression. However, fibre type-specific regulation of AMPK and downstream targets during exercise has not been proven. We hypothesized that AMPK subunits...... (CON) 30 min at 69 ± 1% VO2peak or B) interval cycling (INT) 30 min with 6 × 1.5 min high-intense bouts peaking at 95 ± 2% VO2peak . In type I vs. II fibres a higher β1 AMPK (+215%) and lower γ3 AMPK expression (-71%) was found. α1 , α2 , β2 and γ1 AMPK expression was similar between fibre types...

  1. PPARγ Ligands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    2012-01-01

    Full Text Available In asthma, the increase in airway smooth muscle (ASM can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR. Targetting peroxisome proliferator-activated receptor γ (PPARγ, a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ and pioglitazone (PGZ, inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

  2. NONOates regulate KCl cotransporter-1 and -3 mRNA expression in vascular smooth muscle cells.

    Science.gov (United States)

    Di Fulvio, Mauricio; Lauf, Peter K; Shah, Shalin; Adragna, Norma C

    2003-05-01

    Nitric oxide (NO) donors regulate KCl cotransport (KCC) activity and cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in sheep erythrocytes and in primary cultures of rat vascular smooth muscle cells (VSMCs), respectively. In this study, we used NONOates as rapid and slow NO releasers to provide direct evidence implicating NO as a regulator of KCC3 gene expression at the mRNA level. In addition, we used the expression of KCC3 mRNA to further investigate the mechanism of action of these NO donors at the cellular level. Treatment of VSMCs with rapid NO releasers, like NOC-5 and NOC-9, as well as with the direct NO-independent soluble guanylyl cyclase (sGC) stimulator YC-1, acutely increased KCC3 mRNA expression in a concentration- and time-dependent manner. The slow NO releaser NOC-18 had no effect on KCC3 gene expression. A specific NO scavenger completely prevented the NONOate-induced KCC3 mRNA expression. Inhibition of sGC with LY-83583 blocked the NONOate- and YC-1-induced KCC3 mRNA expression. This study shows that in primary cultures of rat VSMCs, the fast NO releasers NOC-9 and NOC-5, but not the slow NO releaser NOC-18, acutely upregulate KCC3 mRNA expression in a NO/sGC-dependent manner.

  3. Assessment of muscle mass, risk of falls and fear of falling in elderly people with diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Hudson Azevedo Pinheiro

    Full Text Available Abstract Objective : To assess muscle mass, risk of falls and fear of falling in elderly adults with diabetic neuropathy (DNP. Methods : 50 elderly patients with diabetes mellitus (DM and diabetic neuropathy (NPD participated in this study. Risk of falling was assessed using the Berg Balance Scale (BBS. Fear of falling was assessed by means of the Falls Efficacy Scale-International (FES-I. Muscle mass was assessed by tetrapolar bioimpedance analysis (BIA and Janssen's equation. Subjects were divided into two groups: one with a history of falls in the six months before study enrollment (G1 and the other without history of falls (G2. Results : There were statistically significant differences between G1 and G2 regarding lean body mass (p < 0.05, risk of falls as measured by the BBS (p < 0.01, and fear of falling as measured by the FES-I (p < 0.01. In addition, there was a significant correlation between the BBS and BIA (r = 0.45 and p < 0.01, showing that the greater the lean body mass, the lower the risk of falling. Conclusions : We found an association between lean mass, risk of falls and fear of falling in elderly adults with DNP and a history of falls from own height.

  4. The association of low muscle mass with soluble receptor for advanced glycation end products (sRAGE): The Korean Sarcopenic Obesity Study (KSOS).

    Science.gov (United States)

    Kim, Tae Nyun; Park, Man Sik; Lee, Eun Joo; Chung, Hye Soo; Yoo, Hye Jin; Kang, Hyun Joo; Song, Wook; Baik, Sei Hyun; Choi, Kyung Mook

    2018-03-01

    Advanced glycation end products (AGEs) are accumulated with aging in various tissues of humans. The soluble receptor for AGEs (sRAGE) exerts a protective role against the development of aging-related chronic disorders by neutralizing the action of AGEs. We investigated the implication of sRAGE on low muscle mass in Asian men and women. This cross-sectional study included a 390-participant, nondiabetic subcohort recruited within the framework of the Korean Sarcopenic Obesity Study, an ongoing prospective cohort study. Low muscle mass was defined based on the distribution of appendicular skeletal muscle mass divided by body mass index, as proposed by the Foundation for the National Institutes Sarcopenia Project. Serum sRAGE levels were significantly lower in participants with low muscle mass than in participants without low muscle mass (0.76 [0.60-1.00] ng/mL vs 0.87 [0.67-1.15] ng/mL, P = .005). In age- and sex-adjusted correlation analyses, appendicular skeletal muscle mass divided by body mass index was associated with sRAGE (r = 0.109, P = .037). Furthermore, decreased circulating levels of sRAGE are independently associated with low muscle mass (odds ratio = 0.254, P = .002) after adjusting for confounding factors, including insulin resistance and inflammatory markers. The present study shows that a low circulating level of sRAGE may be an independent risk factor for the presence of low muscle mass. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle group specific mechanisms in humans

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Goodmann, Craig; McKenna, Michael J.

    2005-01-01

    Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content......, maximal activity and subunit specific mRNA level (a1, a2, ß1, ß2, ß3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as a1, a2, ß1 and ß2 mRNA levels were higher (P ... increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P Na+,K+ pump content by 18 ± 9% (P

  6. The Regulation of Skeletal Muscle Active Hyperemia: The Differential Role of Adenosine in Muscles of Varied Fiber Types

    Science.gov (United States)

    1986-04-21

    cyclase mediates the coronary relaxation induced by adenosine. Adenosine-induced relaxation is accompanied by cyclic AMP accumulation in bovine ...and the reaction was started by adding 0.01 ml L-glutamic dehydrogenase ( bovine liver; 1200 U•ml-1 in SO% glycerol and vhosphate buffer; p~ 7.4...Physiol: London 68: 213-237, 1929. Dudley, G.A. and R.L. Terjung. Influence of acidosis on AMP deaTIIinase activity in contracting fast-twitch muscle

  7. Feasibility of resistance training in adult McArdle patients: clinical outcomes and muscle strength and mass benefits.

    Science.gov (United States)

    Santalla, Alfredo; Munguía-Izquierdo, Diego; Brea-Alejo, Lidia; Pagola-Aldazábal, Itziar; Díez-Bermejo, Jorge; Fleck, Steven J; Ara, Ignacio; Lucia, Alejandro

    2014-01-01

    We analyzed the effects of a 4-month resistance (weight lifting) training program followed by a 2-month detraining period in 7 adult McArdle patients (5 female) on: muscle mass (assessed by DXA), strength, serum creatine kinase (CK) activity and clinical severity. Adherence to training was ≥84% in all patients and no major contraindication or side effect was noted during the training or strength assessment sessions. The training program had a significant impact on total and lower extremities' lean mass (P training by +855 g (95% confidence interval (CI): 30, 1679) and +547 g (95%CI: 116, 978), respectively, and significantly decreasing with detraining. Body fat showed no significant changes over the study period. Bench press and half-squat performance, expressed as the highest value of average muscle power (W) or force (N) in the concentric-repetition phase of both tests showed a consistent increase over the 4-month training period, and decreased with detraining. Yet muscle strength and power detraining values were significantly higher than pre-training values, indicating that a training effect was still present after detraining. Importantly, all the participants, with no exception, showed a clear gain in muscle strength after the 4-month training period, e.g., bench press: +52 W (95% CI: 13, 91); half-squat: +173 W (95% CI: 96, 251). No significant time effect (P > 0.05) was noted for baseline or post strength assessment values of serum CK activity, which remained essentially within the range reported in our laboratory for McArdle patients. All the patients changed to a lower severity class with training, such that none of them were in the highest disease severity class (3) after the intervention and, as such, they did not have fixed muscle weakness after training. Clinical improvements were retained, in all but one patient, after detraining, such that after detraining all patients were classed as class 1 for disease severity.

  8. Low-Force Muscle Activity Regulates Energy Expenditure after Spinal Cord Injury.

    Science.gov (United States)

    Woelfel, Jessica R; Kimball, Amy L; Yen, Chu-Ling; Shields, Richard K

    2017-05-01

    Reduced physical activity is a primary risk factor for increased morbidity and mortality. People with spinal cord injury (SCI) have reduced activity for a lifetime, as they cannot volitionally activate affected skeletal muscles. We explored whether low-force and low-frequency stimulation is a viable strategy to enhance systemic energy expenditure in people with SCI. This study aimed to determine the effects of low stimulation frequency (1 and 3 Hz) and stimulation intensity (50 and 100 mA) on energy expenditure in people with SCI. We also examined the relationship between body mass index and visceral adipose tissue on energy expenditure during low-frequency stimulation. Ten individuals with complete SCI underwent oxygen consumption monitoring during electrical activation of the quadriceps and hamstrings at 1 and 3 Hz and at 50 and 100 mA. We calculated the difference in energy expenditure between stimulation and rest and estimated the number of days that would be necessary to burn 1 lb of body fat (3500 kcal) for each stimulation protocol (1 vs 3 Hz). Both training frequencies induced a significant increase in oxygen consumption above a resting baseline level (P Energy expenditure positively correlated with stimulus intensity (muscle recruitment) and negatively correlated with adiposity (reflecting the insulating properties of adipose tissue). We estimated that 1 lb of body fat could be burned more quickly with 1 Hz training (58 d) as compared with 3 Hz training (87 d) if an identical number of pulses were delivered. Low-frequency stimulation increased energy expenditure per pulse and may be a feasible option to subsidize physical activity to improve metabolic status after SCI.

  9. Selenium regulates gene expression of selenoprotein W in chicken skeletal muscle system.

    Science.gov (United States)

    Ruan, Hongfeng; Zhang, Ziwei; Wu, Qiong; Yao, Haidong; Li, Jinlong; Li, Shu; Xu, Shiwen

    2012-01-01

    Selenoprotein W (SelW) is abundantly expressed in skeletal muscles of mammals and necessary for the metabolism of skeletal muscles. However, its expression pattern in skeletal muscle system of birds is still uncovered. Herein, to investigate the distribution of SelW mRNA in chicken skeletal muscle system and its response to different selenium (Se) status, 1-day-old chickens were exposed to various concentrations of Se as sodium selenite in the feed for 35 days. In addition, myoblasts were treated with different concentrations of Se in the medium for 72 h. Then the levels of SelW mRNA in skeletal muscles (wing muscle, pectoral muscle, thigh muscle) and myoblasts were determined on days 1, 15, 25, and 35 and at 0, 24, 48, and 72 h, respectively. The results showed that SelW was detected in all these muscle components and it increased both along with the growth of organism and the differentiation process of myoblasts. The thigh muscle is more responsive to Se intake than the other two skeletal muscle tissues while the optimal Se supplementation for SelW mRNA expression in chicken myoblasts was 10(-7) M. In summary, Se plays important roles in the development of chicken skeletal muscles. To effect optimal SelW gene expression, Se must be provided in the diet and the media in adequate amounts and neither at excessive nor deficient levels.

  10. Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system.

    Directory of Open Access Journals (Sweden)

    Theodore P Braun

    Full Text Available Signaling via the type 4-melanocortin receptor (MC4R is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO. We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity.

  11. Regulation of body fat mass by the gut microbiota

    DEFF Research Database (Denmark)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik

    2016-01-01

    New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries...

  12. Association between muscle mass and adipo-metabolic profile: a cross-sectional study in older subjects

    Directory of Open Access Journals (Sweden)

    Perna S

    2015-02-01

    Full Text Available Simone Perna,1,* Davide Guido,2,* Mario Grassi,2 Mariangela Rondanelli1 1Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia, Italy; 2Medical and Genomic Statistics Unit, Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy *These authors contributed equally to this work Background: Sarcopenia, the decrease in muscle mass and function, may lead to various negative health outcomes in elderly. The association among sarcopenia with adiposity and metabolic markers has rarely been studied in the elderly population, with controversial results. The aim of this study is to evaluate this relationship in older subjects.Methods: A cross-sectional study was conducted in 290 elderly patients, focusing on the possible association between muscle mass loss, assessed by relative skeletal muscle mass (RSMM, and an adipo-metabolic profile (AMP defined by adiposity and metabolic biochemical markers. Measurements of body composition were assessed by dual energy X-ray absorptiometry. Biochemical parameters, such as albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, C-reactive protein, and homocysteine and its related markers (folate and vitamin B12 were measured. Using canonical correlation analysis and structural equation modeling, an individual score of AMP was created and correlated with RSMM.Results: The AMP–RSMM correlation was equal to +0.642 (95% confidence interval, +0.512 to +0.773; P<0.001. Hence, a negative association between sarcopenia severity and adiposity/metabolic biochemical markers was highlighted.Conclusion: This study contained a novel way to examine the relationship between the variables of interest based on a composite index of adiposity and metabolic conditions. Results shed light on the orientation and magnitude of

  13. Ratio of Dietary n-6/n-3 Polyunsaturated Fatty Acids Independently Related to Muscle Mass Decline in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Te-Chih Wong

    Full Text Available n-3 polyunsaturated fatty acids (PUFAs might be useful nutritional strategy for treating patients with sarcopenia. We evaluated the effect of the intake of dietary n-3 PUFAs on the skeletal muscle mass (SMM, appendicular skeletal muscle mass (ASM, and its determinants in patients receiving standard hemodialysis (HD treatment for the management of end stage renal disease.In this cross-sectional study, data of 111 HD patients were analyzed. Anthropometric and bioelectrical impedance measurements used to estimate the muscle mass were performed the day of dialysis immediately after the dialysis session. Routine laboratory and 3-day dietary data were also collected. The cutoff value of adequate intake (AI for both n-3 PUFAs and alpha-linolenic acid (ALA was 1.6 g/day and 1.1 g/day for men and women, respectively.The mean age, mean dietary n-3 PUFAs intake, ALA intake, ratio of n-6/n-3 PUFAs intake, SMM, and ASM of patients were 61.4 ± 10.4 years, 2.0 ± 1.3 g/day, 1.5 ± 1.0 g/day, 9.5 ± 6.7 g/day, 23.9 ± 5.5 kg, and 17.5 ± 4.5 kg, respectively. A higher SMM and ASM significantly observed in patients who achieved an AI of n-3 PUFAs. Similar trends appeared to be observed among those patients who achieved the AI of ALA, but the difference was not significantly, except for ASM (P = 0.047. No relevant differences in demographics, laboratory and nutritional parameters were observed, regardless of whether the patients achieved an AI of n-3 PUFAs. Multivariate analysis showed that the BMI and equilibrated Kt/V were independent determinants of the muscle mass. Moreover, the ratio of n-6/n-3 PUFAs was an independent risk determinant of reduced ASM in HD patients.Patients with an AI of n-3 PUFAs had better total-body SMM and ASM. A higher dietary ratio of n-6/n-3 PUFAs seemed to be associated with a reduced muscle mass in HD patients.

  14. Ratio of Dietary n-6/n-3 Polyunsaturated Fatty Acids Independently Related to Muscle Mass Decline in Hemodialysis Patients.

    Science.gov (United States)

    Wong, Te-Chih; Chen, Yu-Tong; Wu, Pei-Yu; Chen, Tzen-Wen; Chen, Hsi-Hsien; Chen, Tso-Hsiao; Yang, Shwu-Huey

    2015-01-01

    n-3 polyunsaturated fatty acids (PUFAs) might be useful nutritional strategy for treating patients with sarcopenia. We evaluated the effect of the intake of dietary n-3 PUFAs on the skeletal muscle mass (SMM), appendicular skeletal muscle mass (ASM), and its determinants in patients receiving standard hemodialysis (HD) treatment for the management of end stage renal disease. In this cross-sectional study, data of 111 HD patients were analyzed. Anthropometric and bioelectrical impedance measurements used to estimate the muscle mass were performed the day of dialysis immediately after the dialysis session. Routine laboratory and 3-day dietary data were also collected. The cutoff value of adequate intake (AI) for both n-3 PUFAs and alpha-linolenic acid (ALA) was 1.6 g/day and 1.1 g/day for men and women, respectively. The mean age, mean dietary n-3 PUFAs intake, ALA intake, ratio of n-6/n-3 PUFAs intake, SMM, and ASM of patients were 61.4 ± 10.4 years, 2.0 ± 1.3 g/day, 1.5 ± 1.0 g/day, 9.5 ± 6.7 g/day, 23.9 ± 5.5 kg, and 17.5 ± 4.5 kg, respectively. A higher SMM and ASM significantly observed in patients who achieved an AI of n-3 PUFAs. Similar trends appeared to be observed among those patients who achieved the AI of ALA, but the difference was not significantly, except for ASM (P = 0.047). No relevant differences in demographics, laboratory and nutritional parameters were observed, regardless of whether the patients achieved an AI of n-3 PUFAs. Multivariate analysis showed that the BMI and equilibrated Kt/V were independent determinants of the muscle mass. Moreover, the ratio of n-6/n-3 PUFAs was an independent risk determinant of reduced ASM in HD patients. Patients with an AI of n-3 PUFAs had better total-body SMM and ASM. A higher dietary ratio of n-6/n-3 PUFAs seemed to be associated with a reduced muscle mass in HD patients.

  15. Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: effect of catalase overexpression.

    Science.gov (United States)

    Barbosa, Marina R; Sampaio, Igor H; Teodoro, Bruno G; Sousa, Thais A; Zoppi, Claudio C; Queiroz, André L; Passos, Madla A; Alberici, Luciane C; Teixeira, Felipe R; Manfiolli, Adriana O; Batista, Thiago M; Cappelli, Ana Paula Gameiro; Reis, Rosana I; Frasson, Danúbia; Kettelhut, Isis C; Parreiras-e-Silva, Lucas T; Costa-Neto, Claudio M; Carneiro, Everardo M; Curi, Rui; Silveira, Leonardo R

    2013-10-01

    The mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Low vitamin D status is associated with reduced muscle mass and impaired physical performance in frail elderly people.

    Science.gov (United States)

    Tieland, M; Brouwer-Brolsma, E M; Nienaber-Rousseau, C; van Loon, L J C; De Groot, L C P G M

    2013-10-01

    Serum 25-hydroxyvitamin D (25(OH)D) status has been associated with muscle mass, strength and physical performance in healthy elderly people. Yet, in pre-frail and frail elderly people this association has not been studied. The objective of this study was to explore the association between vitamin D intake and serum 25(OH)D status with muscle mass, strength and physical performance in a pre-frail and frail elderly population. This cross-sectional study included 127 pre-frail and frail elderly people in The Netherlands. Whole body and appendicular lean mass (ALM) (dual energy X-ray absorptiometry), leg strength (one repetition maximum), handgrip strength and physical performance (short physical performance battery) were measured, and blood samples were collected for the assessment of serum 25(OH)D status (liquid chromatography-tandem mass spectrometry). In addition, habitual dietary intake (3-day food records) and physical activity data (accelerometers) were collected. In total, 53% of the participants had a serum 25(OH)D level below 50  nmol/l. After adjustment for confounding factors, 25(OH)D status was associated with ALM (β=0.012, P=0.05) and with physical performance (β=0.020, PVitamin D intake was associated with physical performance (β=0.18, P0.05). In this frail elderly population, 25(OH)D status is low and suggests a modest association with reduced ALM and impaired physical performance. In addition, vitamin D intake tended to be associated with impaired physical performance. Our findings highlight the need for well-designed intervention trials to assess the impact of vitamin D supplementation on 25(OH)D status, muscle mass and physical performance in pre-frail and frail elderly people.

  17. Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Jing; Lauf, Peter K; Adragna, Norma C

    2003-03-01

    Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

  18. Skeletal myofiber VEGF regulates contraction-induced perfusion and exercise capacity but not muscle capillarity in adult mice.

    Science.gov (United States)

    Knapp, Amy E; Goldberg, Daniel; Delavar, Hamid; Trisko, Breanna M; Tang, Kechun; Hogan, Michael C; Wagner, Peter D; Breen, Ellen C

    2016-07-01

    A single bout of exhaustive exercise signals expression of vascular endothelial growth factor (VEGF) in the exercising muscle. Previous studies have reported that mice with life-long deletion of skeletal myofiber VEGF have fewer capillaries and a severe reduction in endurance exercise. However, in adult mice, VEGF gene deletion conditionally targeted to skeletal myofibers limits exercise capacity without evidence of capillary regression. To explain this, we hypothesized that adult skeletal myofiber VEGF acutely regulates skeletal muscle perfusion during muscle contraction. A tamoxifen-inducible skeletal myofiber-specific VEGF gene deletion mouse (skmVEGF-/-) was used to reduce skeletal muscle VEGF protein by 90% in adult mice. Three weeks after inducing deletion of the skeletal myofiber VEGF gene, skmVEGF-/- mice exhibited diminished maximum running speed (-10%, P Contraction-induced perfusion measured by optical imaging during a period of electrically stimulated muscle contraction was 85% lower in skmVEGF-/- than control mice. No evidence of capillary rarefication was detected in the soleus, gastrocnemius, and extensor digitorum longus (EDL) up to 8 wk after tamoxifen-induced VEGF ablation, and contractility and fatigue resistance of the soleus measured ex vivo were also unchanged. The force-frequency of the EDL showed a small right shift, but fatigue resistance did not differ between EDL from control and skmVEGF-/- mice. These data suggest myofiber VEGF is required for regulating perfusion during periods of contraction and may in this manner affect endurance capacity. Copyright © 2016 the American Physiological Society.

  19. Physical activity as intervention for age-related loss of muscle mass and function

    DEFF Research Database (Denmark)

    Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde

    2016-01-01

    insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer......INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known...... to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative...

  20. TREK-1 Channel Expression in Smooth Muscle as a Target for Regulating Murine Intestinal Contractility: Therapeutic Implications for Motility Disorders

    Directory of Open Access Journals (Sweden)

    Ruolin Ma

    2018-03-01

    Full Text Available Gastrointestinal (GI motility disorders such as irritable bowel syndrome (IBS can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+ channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR, immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.

  1. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models

    Directory of Open Access Journals (Sweden)

    Schiaffino Stefano

    2011-01-01

    Full Text Available Abstract A highly conserved signaling pathway involving insulin-like growth factor 1 (IGF1, and a cascade of intracellular components that mediate its effects, plays a major role in the regulation of skeletal muscle growth. A central component in this cascade is the kinase Akt, also called protein kinase B (PKB, which controls both protein synthesis, via the kinases mammalian target of rapamycin (mTOR and glycogen synthase kinase 3β (GSK3β, and protein degradation, via the transcription factors of the FoxO family. In this paper, we review the composition and function of this pathway in skeletal muscle fibers, focusing on evidence obtained in vivo by transgenic and knockout models and by muscle transient transfection experiments. Although this pathway is essential for muscle growth during development and regeneration, its role in adult muscle response to mechanical load is less clear. A full understanding of the operation of this pathway could help to design molecularly targeted therapeutics aimed at preventing muscle wasting, which occurs in a variety of pathologic contexts and in the course of aging.

  2. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Tieland, C.A.B.; Dirks, M.L.; Zwaluw, van der N.L.; Verdijk, L.; Rest, van de O.; Groot, de C.P.G.M.; Loon, van L.C.

    2012-01-01

    Objectives Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people. Our objective was to assess the impact of protein supplementation on muscle mass, strength, and

  3. Low muscle mass is associated with metabolic syndrome only in nonobese young adults: the Korea National Health and Nutrition Examination Survey 2008-2010.

    Science.gov (United States)

    Kim, Byung Chul; Kim, Mee Kyoung; Han, Kyungdo; Lee, Sae-Young; Lee, Seung-Hwan; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Merchant, Anwar T; Yim, Hyeon Woo; Lee, Won-Chul; Park, Yong Gyu; Park, Yong-Moon

    2015-12-01

    Little is known about the relationship between body composition and metabolic risk factors in young adults. We hypothesized that low muscle mass (LMM) is associated with metabolic syndrome (MetS) and its components in young adults and that the associations vary by obesity. A cross-sectional analysis was conducted using the Korea National Health and Nutrition Examination Survey data. In total, 5300 young adults aged 19 to 39 years were evaluated. Low muscle mass was defined as an appendicular skeletal muscle mass/weight less than 1 SD below the mean for each participant's corresponding sex and age group. Obesity was defined as a body mass index greater than or equal to 25 kg/m2. The prevalence of LMM was higher in obese than nonobese participants (37.6% vs. 9.6%). In the nonobese participants, the prevalence of MetS, high waist circumference, high triglycerides, and high blood pressure was significantly greater in the LMM group than in the high muscle mass group. In the nonobese group, compared with high muscle mass participants, those with LMM had odds ratios for MetS of 3.6 (95% confidence interval, 1.48-8.76; P young adults with LMM may have a high risk of MetS, especially when they are nonobese. Interventions aimed at increasing muscle mass at younger ages may have the potential to reduce MetS. Published by Elsevier Inc.

  4. A systematic review of p53 regulation of oxidative stress in skeletal muscle.

    Science.gov (United States)

    Beyfuss, Kaitlyn; Hood, David A

    2018-12-01

    p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases. Articles published in the English language between January 1, 1990 and March 1, 2017 were identified and isolated based on the analysis of p53 in skeletal muscle in both animal and cell culture models. Literature was categorized according to the modality of imposed oxidative stress including exercise, diet modification, exogenous oxidizing agents, tissue manipulation, irradiation, and hypoxia. With low to moderate levels of oxidative stress, p53 is involved in activating pathways that increase time for cell repair, such as cell cycle arrest and autophagy, to enhance cell survival. However, with greater levels of stress intensity and duration, such as with irradiation, hypoxia, and oxidizing agents, the role of p53 switches to facilitate increased cellular stress levels by initiating DNA fragmentation to induce apoptosis, thereby preventing aberrant cell proliferation. Current evidence confirms that p53 acts as a threshold regulator of cellular homeostasis. Therefore, within each modality, the intensity and duration are parameters of the oxidative stressor that must be analyzed to determine the role p53 plays in regulating signaling pathways to maintain cellular health and function in skeletal muscle. Acadl: acyl-CoA dehydrogenase, long chain; Acadm: acyl-CoA dehydrogenase, C-4 to C-12 straight chain; AIF: apoptosis-inducing factor; Akt: protein kinase B (PKB); AMPK: AMP-activated protein kinase; ATF-4: activating

  5. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte Arneboe; Frandsen, Ulrik; Jensen, Line

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ∼10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  6. Visceral obesity, fat mass/muscle mass ratio and atherogenic dyslipidemia: cross-sectional study. Riobamba, Ecuador

    Directory of Open Access Journals (Sweden)

    Tomas Marcelo Nicolalde Cifuentes

    2015-10-01

    Full Text Available Introduction: The distribution and composition of fat mass is associated with different metabolic risks. The predominance of brown visceral fat is associated with risk factors for cardiovascular disease (CVD, such as: high triglycerides and apolipoprotein B, increased LDL cholesterol, ratio triglycerides/low HDL cholesterol elevated (atherogenic dyslipidemia indicator, insulin resistance, hyperinsulinemia and cardiovascular risk (CVR. Sarcopenia and obesity may act synergistically in functional and metabolic disorders. The aim of this study was to determine the relationship between visceral obesity, fat mass/muscular mass ratio and atherogenic dyslipidemia in adult individuals in order to determine the association pattern between these variables and set strategies for focused attention.Material and Methods: In a sample of 307 subjects of both sexes (21-71 years there was measured atherogenic dyslipidemia as the ratio of triglyceride/HDL cholesterol, visceral obesity measured by bio impedance as the relative score of visceral fat, and the ratio fat mass/lean mass.Results: A cluster analysis was performed to establish the structure of association between these variables with different risk groups. Three groups were identified: the first had visceral obesity with an average relative level of visceral fat of 13.6, the second group with an average of 8.9 and in the third group were placed individuals with the lowest visceral obesity score averaging 6.5. As for the fat mass/lean mas ratio the first two groups had a similar average of this index with a value of 1.56 and 1.69 respectively and the third group with the lowest average value of 1.3. Group 1 presented visceral obesity and impaired fat mass/lean mass ratio and had a high value of triglyceride/HDL ratio 4.1. Group 2 without visceral obesity and a deterioration in the relative fat mass/lean mass ratio had a triglyceride/HDL cholesterol of 3.6 and Group 3; not recorded visceral obesity or

  7. Effect of modified fasting therapy on body weight, fat and muscle mass, and blood chemistry in patients with obesity.

    Science.gov (United States)

    Kim, Koh-Woon; Song, Mi-Yeon; Chung, Seok-Hee; Chung, Won-Seok

    2016-02-01

    The aim of this study was to investigate the effects and safety of modified fasting therapy using fermented medicinal herbs and exercise on body weight, fat and muscle mass, and blood chemistry in obese subjects. Twenty-six patients participated in a 14-day fast, during which they ingested a supplement made from fermented medicinal herbs and carbohydrates (intake: 400-600 kcal/d). The schedule included 7 prefasting relief days and 14 days of stepwise reintroduction of food. The patients also took part in an exercise program that incorporated Qigong, weight training, and walking exercises. The efficacy of treatments was observed by assessing body fat mass and muscle mass, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides in each study period. Specific symptoms or side effects were reported. Body weight and body fat mass both decreased significantly by (5.16 ± 0.95) and (3.89 ± 0.79) kg (both P fasting therapy using fermented medicinal herbs and exercise could be effective and safe on obese patients.

  8. Microtubule Regulation of Kv7 Channels Orchestrates cAMP-Mediated Vasorelaxations in Rat Arterial Smooth Muscle

    DEFF Research Database (Denmark)

    Lindman, Johanna; Khammy, Makhala M; Lundegaard, Pia R

    2018-01-01

    Microtubules can regulate GPCR (G protein-coupled receptor) signaling in various cell types. In vascular smooth muscle, activation of the β-adrenoceptor leads to production of cAMP to mediate a vasorelaxation. Little is known about the role of microtubules in smooth muscle, and given the importance...... of renal and mesenteric arteries that the microtubule stabilizer, paclitaxel, prevented. Sharp microelectrode experiments showed that colchicine treatment caused increased hyperpolarization of mesenteric artery segments in response to isoprenaline. Application of the Kv7 channel blocker, XE991, attenuated...

  9. Lack of independent effect of type 2 diabetes beyond characteristic comorbidities and medications on small muscle mass exercising muscle blood flow and exercise tolerance.

    Science.gov (United States)

    Poitras, Veronica J; Bentley, Robert F; Hopkins-Rosseel, Diana H; LaHaye, Stephen A; Tschakovsky, Michael E

    2015-08-01

    Persons with type 2 diabetes (T2D) are believed to have reduced exercise tolerance; this may be partly due to impaired exercising muscle blood flow (MBF). Whether there is an impact of T2D on exercising MBF within the typical constellation of comorbidities (hypertension, dyslipidemia, obesity) and their associated medications has not been investigated. We tested the hypothesis that small muscle mass exercise tolerance is reduced in persons with T2D versus Controls (matched for age, body mass index, fitness, comorbidities, non-T2D medications) and that this is related to blunted MBF. Eight persons with T2D and eight controls completed a forearm critical force (fCFimpulse) test as a measure of exercise tolerance (10-min intermittent maximal effort forearm contractions; the average contraction impulse in the last 30 sec quantified fCFimpulse). Forearm blood flow (FBF; ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured; forearm vascular conductance (FVK) was calculated. Data are means ± SD, T2D versus Control. fCFimpulse was not different between groups (136.9 ± 47.3  N·sec vs. 163.1 ± 49.7 N·sec, P = 0.371) nor was the ∆FBF from rest to during exercise at fCFimpulse (502.9 ± 144.6 vs. 709.1 ± 289.2 mL/min, P = 0.092), or its determinants ∆FVK and ∆MAP (both P > 0.05), although there was considerable interindividual variability. ∆FBF was strongly related to fCFimpulse (r = 0.727, P = 0.002), providing support for the relationship between oxygen delivery and exercise tolerance. We conclude that small muscle mass exercising MBF and exercise tolerance are not impaired in representative persons with T2D versus appropriately matched controls. This suggests that peripheral vascular control impairment does not contribute to reduced exercise tolerance in this population. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and

  10. Comparison between clinical significance of height-adjusted and weight-adjusted appendicular skeletal muscle mass.

    Science.gov (United States)

    Furushima, Taishi; Miyachi, Motohiko; Iemitsu, Motoyuki; Murakami, Haruka; Kawano, Hiroshi; Gando, Yuko; Kawakami, Ryoko; Sanada, Kiyoshi

    2017-02-13

    This study aimed to compare relationships between height- or weight-adjusted appendicular skeletal muscle mass (ASM/Ht 2 or ASM/Wt) and risk factors for cardiometabolic diseases or osteoporosis in Japanese men and women. Subjects were healthy Japanese men (n = 583) and women (n = 1218). The study population included a young group (310 men and 357 women; age, 18-40 years) and a middle-aged and elderly group (273 men and 861 women; age, ≥41 years). ASM was measured by dual-energy X-ray absorptiometry. The reference values for class 1 and 2 sarcopenia in each sex were defined as values one and two standard deviations below the sex-specific means of the young group, respectively. The reference values for class 1 and 2 sarcopenia defined by ASM/Ht 2 were 7.77 and 6.89 kg/m 2 in men and 6.06 and 5.31 kg/m 2 in women, respectively. The reference values for ASM/Wt were 35.0 and 32.0% in men and 29.6 and 26.4% in women, respectively. In both men and women, ASM/Wt was negatively correlated with higher triglycerides (TG) and positively correlated with serum high-density lipoprotein cholesterol (HDL-C), but these associations were not found in height-adjusted ASM. In women, TG, systolic blood pressure, and diastolic blood pressure in sarcopenia defined by ASM/Wt were significantly higher than those in normal subjects, but these associations were not found in sarcopenia defined by ASM/Ht 2 . Whole-body and regional bone mineral density in sarcopenia defined by ASM/Ht 2 were significantly lower than those in normal subjects, but these associations were not found in sarcopenia defined by ASM/Wt. Weight-adjusted definition was able to identify cardiometabolic risk factors such as TG and HDL-C while height-adjusted definition could identify factors for osteoporosis.

  11. Mechanical muscle function and lean body mass during supervised strength training and testosterone therapy in aging men with low-normal testosterone levels

    DEFF Research Database (Denmark)

    Kvorning, Thue; Christensen, Louise L; Madsen, Klavs

    2013-01-01

    To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study.......To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study....

  12. Sports Mass Age Therapy on the Reduction of Delayed Onset Muscle Soreness of the Quadriceps Femoris

    Directory of Open Access Journals (Sweden)

    Boguszewski Dariusz

    2014-12-01

    Full Text Available Purpose. Massage therapy is one of most commonly applied treatments during athletic training. The aim of this study was to assess the effectiveness of sports massage therapy on reducing post-exercise quadriceps muscle soreness. Methods. A sample of 29 women aged 24-26 years was divided into an experimental group (n = 15 receiving classic sports massage therapy and a control group (n = 14 given no treatment. An exercise session consisting of five sets of deep squat jumps was administered after which lower limb power as assessed via the vertical jump test. Muscle soreness was assessed using the visual analogue scale (VAS and exercise intensity with the Borg Rating of Perceived Exertion Scale. Subsequent measurements of lower limb power and muscle soreness were performed 24, 48, 72 and 96 h after the exercise session. Differences between the measurements were assessed by the Friedman and least significant difference tests while between-group comparisons involved the Mann-Whitney U test. Results. The largest decrease in lower limb power was observed between the first measurement after the exercise session and 24 h later (p < 0.01. The smallest decrease in power was observed in the massage group. The highest levels of muscle soreness were noted 24 h post-exercise in the massage group and 48 h post-exercise in the control group. The experimental group showed a decrease in muscle soreness in each subsequent measurement, with the results close to zero on the VAS 96 h postexercise. Conclusions. Massage therapy quickened recovery and improved muscle efficiency post-exercise and may serve as an effective treatment of muscle soreness. The analgesic effect of massage suggests it should be widely applied in sport, physical therapy and rehabilitation.

  13. Sex and race/ethnic disparities in the cross-sectional association between depressive symptoms and muscle mass: the Multi-ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Remigio-Baker, Rosemay A; Allison, Matthew A; Schreiner, Pamela J; Carnethon, Mercedes R; Nettleton, Jennifer A; Mujahid, Mahasin S; Szklo, Moyses; Crum, Rosa M; Leuotsakos, Jeannie-Marie; Franco, Manuel; Jensky, Nicole; Golden, Sherita Hill

    2015-09-18

    The cross-sectional area of total muscle mass has been reported to decrease by about 40% for those 20-60 years of age. Depressive symptoms may discourage motivation to engage in physical activity such as strength training shown to negate muscle loss. Inflammation related to depressive symptoms may also contribute to muscle atrophy. Physiological differences by sex and race/ethnicity may also modify the association between depression and muscle mass. Evidence on the relationship between depression (or depressive symptoms) and adiposity has been mounting; however, little is known about the depressive symptoms-muscle mass association. We sought to determine the association between elevated depressive symptoms (EDS) and lean muscle mass and whether this varies by sex and race/ethnicity. Evaluating 1605 adults (45-84 years of age) from the Multi-ethnic Study of Atherosclerosis Abdominal Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between EDS (Center for Epidemiologic Studies for Depression Scale score≥16 and/or antidepressant use) and computed tomography-measured abdominal lean muscle mass using linear regression. Muscles were evaluated as a whole and by functionality (locomotion vs. stabilization/posture). Covariates included height, body mass index, sociodemographics, comorbidities, inflammatory markers and health behaviors (pack-years of smoking, alcohol locomotion compared to men, total intentional exercise, daily caloric intake). Sex and race/ethnicity were assessed as potential modifiers. Statistical significance was at a pdepressive symptoms had 5.9 cm2 lower lean muscle mass for locomotion compared to men without EDS, fully-adjusted (CI=-10.5, -1.4, p=0.011). This was statistically significantly different from the null finding among women (interaction p=0.05). Chinese participants with EDS had 10.2 cm2 lower abdominal lean muscle mass for locomotion compared to those without EDS (fully

  14. TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension.

    Science.gov (United States)

    Zeng, Xi; Huang, Ping; Chen, Mingkai; Liu, Shiqian; Wu, Nannan; Wang, Fang; Zhang, Jing

    2018-01-01

    The aim of the present study was to elucidate the effect of transmembrane protein 16A (TMEM16A) on portal vein smooth muscle cell (PVSMC) proliferation associated with portal vein remodeling in portal hypertension (PHT). Sprague-Dawley rats were subjected to bile duct ligation to establish a rat model of liver cirrhosis and PHT. Sham-operated animals served as controls. At 8 weeks after bile duct ligation, the extent of liver fibrosis and the portal vein wall thickness were assessed using hematoxylin-eosin staining. The protein expression levels of TMEM16A, extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) in the portal vein were detected by immunohistochemistry and western blotting. In vitro , the lentivirus vectors were constructed and transfected into PVSMCs to upregulate the expression of TMEM16A. Isolated rat primary PVSMCs were treated with a small molecule inhibitor of TMEM16A, T16A-inhA01. Cell cycle was detected by flow cytometry. The activity of TMEM16A in the portal vein isolated from bile duct ligated rats was decreased, while the expression level of p-ERK1/2 was increased. However, in vitro , upregulation of TMEM16A promoted the proliferation PVSMCs, while inhibition of TMEM16A channels inhibited the proliferation of PVSMCs. The results indicated that TMEM16A contributes to PVSMCs proliferation in vitro , but in vivo , it may be a negative regulator of cell proliferation influenced by numerous factors.

  15. Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

    Directory of Open Access Journals (Sweden)

    Juan Rodríguez-Vita

    Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

  16. Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

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    Li, W. [School of Control Science and Engineering, Biomedical Engineering Institute, Shandong University, Jinan, Shandong (China); Kong, Q.Y.; Zhao, C.F. [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong (China); Zhao, F. [Department of Medicine, Weill Medical College of Cornell University, New York, NY (United States); Li, F.H.; Xia, W. [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong (China); Wang, R. [Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong (China); Hu, Y.M. [School of Control Science and Engineering, Biomedical Engine