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Myostatin human

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https://www.readbyqxmd.com/read/28432282/loss-of-function-myostatin-mutation-increases-insulin-sensitivity-and-browning-of-white-fat-in-meishan-pigs
#1
Chunbo Cai, Lili Qian, Shengwang Jiang, Youde Sun, Qingqing Wang, Dezun Ma, Gaojun Xiao, Biao Li, Shanshan Xie, Ting Gao, Yaoxing Chen, Jie Liu, Xiaorong An, Wentao Cui, Kui Li
Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn -/- ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411009/skeletal-muscle-morphology-and-regulatory-signalling-in-endurance-trained-and-sedentary-individuals-the-influence-of-ageing
#2
U R Mikkelsen, J Agergaard, C Couppé, J F Grosset, A Karlsen, S P Magnusson, P Schjerling, M Kjaer, A L Mackey
Muscle mass in humans is inversely associated with circulating levels of inflammatory cytokines, but the interaction between ageing and training on muscle composition and the intra-muscular signalling behind inflammation and contractile protein synthesis and degradation is unknown. We studied 15 healthy life-long endurance runners, 12 age-matched untrained controls, 10 young trained and 12 young untrained individuals. Thigh muscle composition was investigated by magnetic resonance imaging (MRI), where non-contractile intramuscular tissue (NCIT) area (fat and connective tissue) was found to be greater in older but lower in trained individuals...
April 11, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28406165/myostatin-mediates-abdominal-aortic-atherosclerosis-progression-by-inducing-vascular-smooth-muscle-cell-dysfunction-and-monocyte-recruitment
#3
D Verzola, S Milanesi, M Bertolotto, S Garibaldi, B Villaggio, C Brunelli, M Balbi, P Ameri, F Montecucco, D Palombo, G Ghigliotti, G Garibotto, J H Lindeman, C Barisione
Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345488/deep-infiltrating-endometriosis-and-endometrial-adenocarcinoma-express-high-levels-of-myostatin-and-its-receptors-messenger-rnas
#4
Patrizia Carrarelli, Lucia Funghi, Pasquapina Ciarmela, Gabriele Centini, Fernando M Reis, Cynthia Dela Cruz, Alberto Mattei, Silvia Vannuccini, Felice Petraglia
Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28339962/fstl3-is-increased-in-renal-dysfunction
#5
Susan Kralisch, Annett Hoffmann, Nora Klöting, Anette Bachmann, Jürgen Kratzsch, Jens-Uwe Stolzenburg, Anja Dietel, Joachim Beige, Matthias Anders, Ingolf Bast, Matthias Blüher, Ming-Zhi Zhang, Raymond C Harris, Michael Stumvoll, Mathias Fasshauer, Thomas Ebert
Background.: Follistatin-like 3 (FSTL3) is a novel cytokine that regulates insulin sensitivity and counteracts activin/myostatin signalling. In the present study, regulation of FSTL3 in renal dysfunction was investigated in both human chronic kidney disease (CKD) and acute kidney dysfunction (AKD). Furthermore, mFSTL3 expression was analysed in insulin-sensitive tissues in a mouse model of CKD. Methods.: Circulating FSTL3 was quantified by enzyme-linked immunosorbent assay in 581 patients with CKD covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5...
March 3, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28202082/bone-morphogenetic-proteins-and-myostatin-pathways-key-mediator-of-human-sarcopenia
#6
Manuel Scimeca, Eleonora Piccirilli, Francesca Mastrangeli, Cecilia Rao, Maurizio Feola, Augusto Orlandi, Elena Gasbarra, Elena Bonanno, Umberto Tarantino
BACKGROUND: Sarcopenia, osteoporosis and osteoarthritis are the most frequent musculoskeletal disorders affecting older people. The main aim of this study was to test the hypothesis that the balance between BMPs and myostatin pathways regulates the age-related muscle degeneration in OP and OA patients. To this end, we investigated the relationship among the expression of BMP-2/4-7, myostatin and phosphorylated Smads1-5-8 and the muscle quality, evaluated in term of fibers atrophy and satellite cells activity...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28101649/molecular-mechanism-of-sarcopenia-and-cachexia-recent-research-advances
#7
REVIEW
Kunihiro Sakuma, Wataru Aoi, Akihiko Yamaguchi
Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules...
January 19, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28027451/the-use-of-platelet-rich-and-platelet-poor-plasma-to-enhance-differentiation-of-skeletal-myoblasts-implications-for-the-use-of-autologous-blood-products-for-muscle-regeneration
#8
Olga Miroshnychenko, Wen-Teh Chang, Jason L Dragoo
BACKGROUND: Platelet-rich plasma (PRP) has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP does not show a consistent clinical effect. Purpose/Hypothesis: This study aimed to compare the effects of the following non-neutrophil-containing (leukocyte-poor) plasma fractions on human skeletal muscle myoblast (HSMM) differentiation: (1) PRP, (2) modified PRP (Mod-PRP), in which transforming growth factor β1 (TGF-β1) and myostatin (MSTN) were depleted, and (3) platelet-poor plasma (PPP)...
March 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/27932674/metabolic-adaptations-in-skeletal-muscle-after-84-days-of-bed-rest-with-and-without-concurrent-flywheel-resistance-exercise
#9
José M Irimia, Mario Guerrero, Paula Rodriguez-Miguelez, Joan A Cadefau, Per A Tesch, Roser Cussó, Rodrigo Fernandez-Gonzalo
As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α), and myostatin, were analyzed in samples from m...
January 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27906065/dystrophin-deficient-dogs-with-reduced-myostatin-have-unequal-muscle-growth-and-greater-joint-contractures
#10
Joe N Kornegay, Daniel J Bogan, Janet R Bogan, Jennifer L Dow, Jiahui Wang, Zheng Fan, Naili Liu, Leigh C Warsing, Robert W Grange, Mihye Ahn, Cynthia J Balog-Alvarez, Steven W Cotten, Monte S Willis, Candice Brinkmeyer-Langford, Hongtu Zhu, Joe Palandra, Carl A Morris, Martin A Styner, Kathryn R Wagner
BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition...
April 4, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905294/glucocorticoids-increase-skeletal-muscle-nf-%C3%AE%C2%BAb-inducing-kinase-nik-links-to-muscle-atrophy
#11
Christopher S Fry, Syed Z Nayeem, Edgar L Dillon, Partha S Sarkar, Batbayar Tumurbaatar, Randall J Urban, Traver J Wright, Melinda Sheffield-Moore, Ronald G Tilton, Sanjeev Choudhary
Glucocorticoids (GC) are a frontline therapy for numerous acute and chronic diseases because of their demonstrated efficacy at reducing systemic inflammation. An unintended side effect of GC therapy is the stimulation of skeletal muscle atrophy. Pathophysiological mechanisms responsible for GC-induced skeletal muscle atrophy have been extensively investigated, and the ability to treat patients with GC without unintended muscle atrophy has yet to be realized. We have reported that a single, standard-of-care dose of Methylprednisolone increases in vivo expression of NF-κB-inducing kinase (NIK), an important upstream regulatory kinase controlling NF-κB activation, along with other key muscle catabolic regulators such as Atrogin-1 and MuRF1 that induce skeletal muscle proteolysis...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27787698/the-transgenic-expression-of-human-follistatin-344-increases-skeletal-muscle-mass-in-pigs
#12
Fei Chang, Rui Fang, Meng Wang, Xin Zhao, Wen Chang, Zaihu Zhang, Ning Li, Qingyong Meng
Follistatin (FST), which was first found in the follicles of cattle and pigs, has been shown to be an essential regulator for muscle development. Mice that were genetically engineered to overexpress Fst specifically in muscle had at least twice the amount of skeletal muscle mass as controls; these findings are similar to earlier results obtained in myostatin-knockout mice. However, the role of follistatin in skeletal muscle development has yet to be clarified in livestock. Here, we describe transgenic Duroc pigs that exogenously express Fst specifically in muscle tissue...
February 2017: Transgenic Research
https://www.readbyqxmd.com/read/27700008/translational-pharmacokinetic-pharmacodynamic-analysis-of-myo-029-antibody-for-muscular-dystrophy
#13
P Singh, H Rong, T Gordi, J Bosley, I Bhattacharya
Suppression of the myostatin (GDF-8) pathway has emerged as an important therapeutic paradigm for muscle-wasting disorders. In this study, we conducted a translational pharmacokinetic/pharmacodynamic (PK/PD) analysis of MYO-029, an anti-myostatin monoclonal antibody, using PK data in mice, rats, monkeys, humans, mouse tissue distribution data with (125) I-labeled MYO-029, muscle weight increase in SCID mice, and muscle circumference changes in monkeys. This analysis revealed significant in vivo potency shift between mice and monkeys (72 nM vs...
December 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27695802/invited-review-inhibitors-of-myostatin-as-methods-of-enhancing-muscle-growth-and-development
#14
REVIEW
P R Chen, K Lee
With the increasing demand for affordable, high-quality meat, livestock and poultry producers must continually find ways to maximize muscle growth in their animals without compromising palatability of the meat products. Muscle mass relies on myoblast proliferation during prenatal or prehatch stages and fiber hypertrophy through protein synthesis and nuclei donation by satellite cells after birth or hatch. Therefore, understanding the cellular and molecular mechanisms of myogenesis and muscle development is of great interest...
August 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27625211/beyond-cdr-grafting-structure-guided-humanization-of-framework-and-cdr-regions-of-an-anti-myostatin-antibody
#15
James R Apgar, Michelle Mader, Rita Agostinelli, Susan Benard, Peter Bialek, Mark Johnson, Yijie Gao, Mark Krebs, Jane Owens, Kevin Parris, Michael St Andre, Kris Svenson, Carl Morris, Lioudmila Tchistiakova
Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies...
October 2016: MAbs
https://www.readbyqxmd.com/read/27559042/glycoproteomics-reveals-decorin-peptides-with-anti-myostatin-activity-in-human-atrial-fibrillation
#16
Javier Barallobre-Barreiro, Shashi K Gupta, Anna Zoccarato, Rika Kitazume-Taneike, Marika Fava, Xiaoke Yin, Tessa Werner, Marc N Hirt, Anna Zampetaki, Alessandro Viviano, Mei Chong, Marshall Bern, Antonios Kourliouros, Nieves Domenech, Peter Willeit, Ajay M Shah, Marjan Jahangiri, Liliana Schaefer, Jens W Fischer, Renato V Iozzo, Rosa Viner, Thomas Thum, Joerg Heineke, Antoine Kichler, Kinya Otsu, Manuel Mayr
BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS: Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides. RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed...
September 13, 2016: Circulation
https://www.readbyqxmd.com/read/27467217/effect-of-resistance-exercise-intensity-on-the-expression-of-pgc-1%C3%AE-isoforms-and-the-anabolic-and-catabolic-signaling-mediators-igf-1-and-myostatin-in-human-skeletal-muscle
#17
Neil A Schwarz, Sarah K McKinley-Barnard, Mike B Spillane, Thomas L Andre, Joshua J Gann, Darryn S Willoughby
The purpose of this study was to investigate the acute messenger (mRNA) expression of the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) isoforms, insulin-like growth factor-1Ea (IGF-1Ea), and myostatin in response to 2 resistance exercise intensities. In a uniform-balanced, crossover design, 10 participants performed 2 separate testing sessions involving a lower body resistance exercise component consisting of a lower intensity (50% of 1-repetition maximum; 1RM) protocol and a higher intensity (80% of 1RM) protocol of equal volumes...
August 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/27304512/quantification-of-gdf11-and-myostatin-in-human-aging-and-cardiovascular-disease
#18
Marissa J Schafer, Elizabeth J Atkinson, Patrick M Vanderboom, Brian Kotajarvi, Thomas A White, Matthew M Moore, Charles J Bruce, Kevin L Greason, Rakesh M Suri, Sundeep Khosla, Jordan D Miller, H Robert Bergen, Nathan K LeBrasseur
Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions...
June 14, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27293072/characterizing-the-molecular-phenotype-of-an-atp7a-t985i-conditional-knock-in-mouse-model-for-x-linked-distal-hereditary-motor-neuropathy-dhmnx
#19
Gonzalo Perez-Siles, Adrienne Grant, Melina Ellis, Carolyn Ly, Aditi Kidambi, Mamdouh Khalil, Roxana M Llanos, Sharon La Fontaine, Alleene V Strickland, Stephan Züchner, Sandra Bermeo, Elysia Neist, Tara C Brennan-Speranza, Reinaldo I Takata, Carlos E Speck-Martins, Julian F B Mercer, Garth A Nicholson, Marina L Kennerson
ATP7A is a P-type ATPase essential for cellular copper (Cu) transport and homeostasis. Loss-of-function ATP7A mutations causing systemic Cu deficiency are associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome. We previously identified two rare ATP7A missense mutations (P1386S and T994I) leading to a non-fatal form of motor neuron disorder, X-linked distal hereditary motor neuropathy (dHMNX), without overt signs of systemic Cu deficiency. Recent investigations using a tissue specific Atp7a knock out model have demonstrated that Cu plays an essential role in motor neuron maintenance and function, however the underlying pathogenic mechanisms of ATP7A mutations causing axonal degeneration remain unknown...
September 1, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27245339/formoterol-decreases-muscle-wasting-as-well-as-inflammation-in-the-rat-model-of-rheumatoid-arthritis
#20
Ana Belén Gómez-SanMiguel, Carolina Gomez-Moreira, María Paz Nieto-Bona, Carmen Fernández-Galaz, Maria Ángeles Villanúa, Ana Isabel Martín, Asunción López-Calderón
Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant...
June 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
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