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https://www.readbyqxmd.com/read/27922496/metabolic-myopathies
#1
Mark A Tarnopolsky
PURPOSE OF REVIEW: Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. RECENT FINDINGS: The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27922100/evaluation-of-candidate-reference-genes-for-rt-qpcr-studies-in-three-metabolism-related-tissues-of-mice-after-caloric-restriction
#2
Huan Gong, Liang Sun, Beidong Chen, Yiwen Han, Jing Pang, Wei Wu, Ruomei Qi, Tie-Mei Zhang
Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) is a routine method for gene expression analysis, and reliable results depend on proper normalization by stable reference genes. Caloric restriction (CR) is a robust lifestyle intervention to slow aging and delay onset of age-associated diseases via inducing global changes in gene expression. Reliable normalization of RT-qPCR data becomes crucial in CR studies. In this study, the expression stability of 12 candidate reference genes were evaluated in inguinal white adipose tissue (iWAT), skeletal muscle (Sk...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916644/targeted-mitochondrial-uncoupling-beyond-ucp1-the-fine-line-between-death-and-metabolic-health
#3
REVIEW
Mario Ost, Susanne Keipert, Susanne Klaus
In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916530/enhanced-respiratory-chain-supercomplex-formation-in-response-to-exercise-in-human-skeletal-muscle
#4
Chiara Greggio, Pooja Jha, Sameer S Kulkarni, Sylviane Lagarrigue, Nicholas T Broskey, Marie Boutant, Xu Wang, Sonia Conde Alonso, Emmanuel Ofori, Johan Auwerx, Carles Cantó, Francesca Amati
Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiovascular complications. Here, we investigated the effect of 4 months of exercise training on skeletal muscle mitochondria electron transport chain complexes and supercomplexes in 26 healthy, sedentary older adults. Exercise differentially modulated respiratory complexes...
November 28, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27913948/branched-chain-amino-acids-administration-suppresses-endurance-exercise-related-activation-of-ubiquitin-proteasome-signaling-in-trained-human-skeletal-muscle
#5
Evgeny A Lysenko, Tatiana F Vepkhvadze, Egor M Lednev, Olga L Vinogradova, Daniil V Popov
We tested whether post exercise ingestion of branched-chain amino acids (BCAA < 10 g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1 g/kg). Post exercise ACC(Ser79/222) phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P < 0...
December 3, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27913098/succinyl-coa-synthetase-sucla2-deficiency-in-two-siblings-with-impaired-activity-of-other-mitochondrial-oxidative-enzymes-in-skeletal-muscle-without-mitochondrial-dna-depletion
#6
Xiaoping Huang, Jirair K Bedoyan, Didem Demirbas, David J Harris, Alexander Miron, Simone Edelheit, George Grahame, Suzanne D DeBrosse, Lee-Jun Wong, Charles L Hoppel, Douglas S Kerr, Irina Anselm, Gerard T Berry
Mutations in SUCLA2 result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) (A-SCS) deficiency, a mitochondrial tricarboxylic acid cycle disorder. The phenotype associated with this gene defect is largely encephalomyopathy. We describe two siblings compound heterozygous for SUCLA2 mutations, c.985A>G (p.M329V) and c.920C>T (p.A307V), with parents confirmed as carriers of each mutation. We developed a new LC-MS/MS based enzyme assay to demonstrate the decreased SCS activity in the siblings with this unique genotype...
November 12, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27899900/fiber-type-specific-satellite-cell-content-in-cyclists-following-heavy-training-with-carbohydrate-and-carbohydrate-protein-supplementation
#7
Alec I McKenzie, Andrew C D'Lugos, Michael J Saunders, Keith D Gworek, Nicholas D Luden
The central purpose of this study was to evaluate the fiber type-specific satellite cell and myonuclear responses of endurance-trained cyclists to a block of intensified training, when supplementing with carbohydrate (CHO) vs. carbohydrate-protein (PRO). In a crossover design, endurance-trained cyclists (n = 8) performed two consecutive training periods, once supplementing with CHO (de facto "control" condition) and the other with PRO. Each training period consisted of 10 days of intensified cycle training (ICT-120% increase in average training duration) followed by 10 days of recovery (RVT-reduced volume training; 33% volume reduction vs...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27899419/progressive-cl-channel-defects-reveal-disrupted-skeletal-muscle-maturation-in-r6-2-huntington-s-mice
#8
Daniel R Miranda, Monica Wong, Shannon H Romer, Cynthia McKee, Gabriela Garza-Vasquez, Alyssa C Medina, Volker Bahn, Andrew D Steele, Robert J Talmadge, Andrew A Voss
Huntington's disease (HD) patients suffer from progressive and debilitating motor dysfunction. Previously, we discovered reduced skeletal muscle chloride channel (ClC-1) currents, inwardly rectifying potassium (Kir) channel currents, and membrane capacitance in R6/2 transgenic HD mice. The ClC-1 loss-of-function correlated with increased aberrant mRNA processing and decreased levels of full-length ClC-1 mRNA (Clcn1 gene). Physiologically, the resulting muscle hyperexcitability may help explain involuntary contractions of HD...
November 29, 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27897439/il-4-mrna-is-downregulated-in-the-liver-of-pancreatic-cancer-patients-suffering-from-cachexia
#9
Olga Prokopchuk, Jürgen M Steinacker, Ulrich Nitsche, Stephanie Otto, Jeannine Bachmann, Elaine C Schubert, Helmut Friess, Marc E Martignoni
BACKGROUND: Interleukin-4 (IL-4) together with interleukin-13 (IL-13) play an important role in inflammation and wound repair, and are known to be upregulated in human skeletal muscle after strenuous physical exercise. Additionally, these cytokines may act as autocrine growth factors in pancreatic cancer cells. We hypothesize that IL-4, IL-13, and their corresponding receptors are involved in mechanism of cancer cachexia. METHODS: Tissue samples from human skeletal muscle, white fat, liver, healthy pancreas, and pancreatic ductal adenocarcinoma were analyzed by quantitative real-time polymerase chain reaction for mRNA expression levels of IL-4, IL-13, IL-4 receptor α, and IL-13 receptor α1...
November 29, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27897407/activin-a-induces-skeletal-muscle-catabolism-via-p38%C3%AE-mitogen-activated-protein-kinase
#10
Hui Ding, Guohua Zhang, Ka Wai Thomas Sin, Zhelong Liu, Ren-Kuo Lin, Min Li, Yi-Ping Li
BACKGROUND: Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined. METHODS: We investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically...
September 16, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897402/the-impact-of-ageing-physical-activity-and-pre-frailty-on-skeletal-muscle-phenotype-mitochondrial-content-and-intramyocellular-lipids-in-men
#11
Félix St-Jean-Pelletier, Charlotte H Pion, Jean-Philippe Leduc-Gaudet, Nicolas Sgarioto, Igor Zovilé, Sébastien Barbat-Artigas, Olivier Reynaud, Feras Alkaterji, François C Lemieux, Alexis Grenon, Pierrette Gaudreau, Russell T Hepple, Stéphanie Chevalier, Marc Belanger, José A Morais, Mylène Aubertin-Leheudre, Gilles Gouspillou
BACKGROUND: The exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men. METHODS: Recreationally active young adult (20-30 yo; YA); active (ACT) and sedentary (SED) middle-age (50-65 yo; MA-ACT and MA-SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre-frail older (65 + PF) men were recruited...
September 2, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27896430/myosin-light-chain-phosphorylation-is-required-for-peak-power-output-of-mouse-fast-skeletal-muscle-in-vitro
#12
Joshua Bowslaugh, William Gittings, Rene Vandenboom
The skeletal myosin light chain kinase (skMLCK) catalyzed phosphorylation of the myosin regulatory light chain (RLC) is associated with potentiation of force, work, and power in rodent fast twitch muscle. The purpose of this study was to compare concentric responses of EDL from wild-type (WT) and skMLCK devoid (skMLCK(-/-)) muscles at a range of shortening speeds (0.05 to 0.70 V max) around that expected to produce maximal power (in vitro, 25 °C) both before (unpotentiated) and after (potentiated) a potentiating stimulus (PS)...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27892898/the-role-of-adipose-tissue-and-excess-of-fatty-acids-in-the-induction-of-insulin-resistance-in-skeletal-muscle
#13
Agnieszka Błachnio-Zabielska, Sławomir Grycel, Marta Chacińska, Piotr Zabielski
Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD) and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes) and type 2 diabetes (T2D). The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG) is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramides (Cer)...
November 14, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27892461/liver-specific-atp-citrate-lyase-inhibition-by-bempedoic-acid-decreases-ldl-c-and-attenuates-atherosclerosis
#14
Stephen L Pinkosky, Roger S Newton, Emily A Day, Rebecca J Ford, Sarka Lhotak, Richard C Austin, Carolyn M Birch, Brennan K Smith, Sergey Filippov, Pieter H E Groot, Gregory R Steinberg, Narendra D Lalwani
Despite widespread use of statins to reduce low-density lipoprotein cholesterol (LDL-C) and associated atherosclerotic cardiovascular risk, many patients do not achieve sufficient LDL-C lowering due to muscle-related side effects, indicating novel treatment strategies are required. Bempedoic acid (ETC-1002) is a small molecule intended to lower LDL-C in hypercholesterolemic patients, and has been previously shown to modulate both ATP-citrate lyase (ACL) and AMP-activated protein kinase (AMPK) activity in rodents...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27890887/royal-jelly-improves-hyperglycemia-in-obese-diabetic-kk-ay-mice
#15
Mei Yoshida, Kaori Hayashi, Risa Watadani, Yoshiyasu Okano, Keiya Tanimura, Jun Kotoh, Daiki Sasaki, Kozo Matsumoto, Akihiko Maeda
The study examined whether royal jelly (RJ) can prevent obesity and ameliorate hyperglycemia in type 2 diabetes. This study utilized obese/diabetic KK-Ay mice. RJ (10 mg/kg) was administered by oral gavage. Body weight, plasma glucose and insulin levels were measured. mRNA and protein levels were determined using quantitative reverse transcription polymerase chain reaction and western blotting, respectively. Four weeks of RJ administration improved hyperglycemia and partially suppressed body weight gain, although the latter effect did not reach statistical significance...
November 26, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27888539/macrophage-depletion-impairs-skeletal-muscle-regeneration-the-roles-of-regulatory-factors-for-muscle-regeneration
#16
Xiaoguang Liu, Yu Liu, Linlin Zhao, Zhigang Zeng, Weihua Xiao, Peijie Chen
Though macrophages are essential for skeletal muscle regeneration, which is a complex process, the roles and mechanisms of the macrophages in the process of muscle regeneration are still not fully understood. The objective of this study is to explore the roles of macrophages and the mechanisms involved in the regeneration of injured skeletal muscle. One hundred and twelve C57BL/6 mice were randomly divided into muscle contusion and macrophages depleted groups. Their gastrocnemius muscles were harvested at the time points of 12h, 1, 3, 5, 7, 14d post-injury...
November 26, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27886623/liver-bcatm-transgenic-mouse-model-reveals-the-important-role-of-the-liver-in-maintaining-bcaa-homeostasis
#17
Elitsa A Ananieva, Cynthia G Van Horn, Meghan R Jones, Susan M Hutson
Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted...
November 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27878977/silk-fibroin-scaffolds-with-muscle-like-elasticity-support-in-vitro-differentiation-of-human-skeletal-muscle-cells
#18
Vishal Chaturvedi, Deboki Naskar, Beverley F Kinnear, Elizabeth Grenik, Danielle E Dye, Miranda D Grounds, Subhas C Kundu, Deirdre R Coombe
Human adult skeletal muscle has a limited ability to regenerate after injury and therapeutic options for volumetric muscle loss are few. Technologies to enhance regeneration of tissues generally rely upon bioscaffolds to mimic aspects of the tissue extracellular matrix (ECM). In the present study, silk fibroins from four Lepidoptera (silkworm) species engineered into three-dimensional scaffolds were examined for their ability to support the differentiation of primary human skeletal muscle myoblasts. Human skeletal muscle myoblasts (HSMMs) adhered, spread and deposited extensive ECM on all the scaffolds, but immunofluorescence and quantitative polymerase chain reaction analysis of gene expression revealed that myotube formation occurred differently on the various scaffolds...
November 22, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27878731/effect-of-cardiomyopathic-mutations-in-tropomyosin-on-calcium-regulation-of-the-actin-myosin-interaction-in-skeletal-muscle
#19
G V Kopylova, D V Shchepkin, D I Borovkov, A M Matyushenko
Tropomyosin plays an important role in the regulation of actin-myosin interaction in striated muscles. Mutations in the tropomyosin gene disrupt actin-myosin interaction and lead to myopathies and cardiomyopathies. Tropomyosin with mutations in the α-chain is expressed in both the myocardium and skeletal muscles. We studied the effect of mutations in the α-chain of tropomyosin related to hypertrophic (D175N and E180G) and dilated cardiomyopathies (E40K and E54K) on calcium regulation of the actin-myosin interaction in skeletal muscles...
November 23, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27875996/differences-in-the-skeletal-muscle-transcriptome-profile-associated-with-extreme-values-of-fatty-acids-content
#20
Aline S M Cesar, Luciana C A Regitano, Mirele D Poleti, Sónia C S Andrade, Polyana C Tizioto, Priscila S N Oliveira, Andrezza M Felício, Michele L do Nascimento, Amália S Chaves, Dante P D Lanna, Rymer R Tullio, Renata T Nassu, James E Koltes, Eric Fritz-Waters, Gerson B Mourão, Adhemar Zerlotini-Neto, James M Reecy, Luiz L Coutinho
BACKGROUND: Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle...
November 22, 2016: BMC Genomics
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