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Carbohydrates and lipids provide the majority of substrates to fuel mitochondrial oxidative phosphorylation. Metabolic inflexibility, defined as an impaired ability to switch between these fuels, is implicated in a number of metabolic diseases. Here, we explore the mechanism by which physical inactivity promotes metabolic inflexibility in skeletal muscle. We developed a mouse model of sedentariness, small mouse cage (SMC), that, unlike other classic models of disuse in mice, faithfully recapitulated metabolic responses that occur in humans. Bioenergetic phenotyping of skeletal muscle mitochondria displayed metabolic inflexibility induced by physical inactivity, demonstrated by a reduction in pyruvate- stimulated respiration ([JO.sub.2]) in the absence of a change in palmitate-stimulated [JO.sub.2]. Pyruvate resistance in these mitochondria was likely driven by a decrease in phosphatidylethanolamine (PE) abundance in the mitochondrial membrane. Reduction in mitochondrial PE by heterozygous deletion of phosphatidylserine decarboxylase (PSD) was sufficient to induce metabolic inflexibility measured at the whole-body level, as well as at the level of skeletal muscle mitochondria. Low mitochondrial PE in C2C12 myotubes was sufficient to increase glucose flux toward lactate. We further implicate that resistance to pyruvate metabolism is due to attenuated mitochondrial entry via mitochondrial pyruvate carrier (MPC). These findings suggest a mechanism by which mitochondrial PE directly regulates MPC activity to modulate metabolic flexibility in mice., Introduction Chronic physical inactivity increases all-cause mortality by 30%, accounting for one death every 44 seconds (1-4). Sedentary behavior exacerbates the risk for many chronic diseases, such as type 2 [...]

Byline: Ankur. Vivek, Pratishtha. Sengar, Rameshwar. Chaurasia, Abhishek. Pathak, Anand. Kumar, Varun. Singh Dear Sir, Acute, generalized, muscle paralysis in a young and healthy individual causes much distress.[1] Periodic paralysis [...]

Byline: N. Ceylan, S. Koca , I. Yavas and A. A. Cenesiz Keywords: broiler; bone mineralization; calcium and phosphorus levels; performance INTRODUCTION Ca (calcium) and P (phosphorus) are two main [...]

Skeletal muscle regenerates through the activation of resident stem cells. Termed satellite cells, these normally quiescent cells are induced to proliferate by wound-derived signals.sup.1. Identifying the source and nature of these cues has been hampered by an inability to visualize the complex cell interactions that occur within the wound. Here we use muscle injury models in zebrafish to systematically capture the interactions between satellite cells and the innate immune system after injury, in real time, throughout the repair process. This analysis revealed that a specific subset of macrophages 'dwell' within the injury, establishing a transient but obligate niche for stem cell proliferation. Single-cell profiling identified proliferative signals that are secreted by dwelling macrophages, which include the cytokine nicotinamide phosphoribosyltransferase (Nampt, which is also known as visfatin or PBEF in humans). Nampt secretion from the macrophage niche is required for muscle regeneration, acting through the C-C motif chemokine receptor type 5 (Ccr5), which is expressed on muscle stem cells. This analysis shows that in addition to their ability to modulate the immune response, specific macrophage populations also provide a transient stem-cell-activating niche, directly supplying proliferation-inducing cues that govern the repair process that is mediated by muscle stem cells. This study demonstrates that macrophage-derived niche signals for muscle stem cells, such as NAMPT, can be applied as new therapeutic modalities for skeletal muscle injury and disease. Specific macrophage populations provide a transient niche that activates muscle stem cells after muscle injury and supply proliferation-inducing cues that govern the repair process mediated by these cells in both zebrafish and mouse injury models., Author(s): Dhanushika Ratnayake [sup.1] [sup.2] , Phong D. Nguyen [sup.3] [sup.4] , Fernando J. Rossello [sup.1] [sup.5] , Verena C. Wimmer [sup.6] [sup.7] , Jean L. Tan [sup.1] [sup.2] , [...]

Epigenetic DNA methylation (1-carbon metabolism) is crucial for gene imprinting/off-printing that ensures epigenetic memory but also generates a copious amount of homocysteine (Hcy), unequivocally. That is why during pregnancy, expectant mothers are recommended 'folic acid' preemptively to avoid birth defects in the young ones because of elevated Hcy levels (i.e., hyperhomocysteinemia (HHcy)). As we know, children born with HHcy have several musculoskeletal abnormalities, including growth retardation. Here, we focus on the gut-dysbiotic microbiome implication(s) that we believe instigates the '1-carbon metabolism' and HHcy causing growth retardation along with skeletal muscle abnormalities. We test our hypothesis whether high-methionine diet (HMD) (an amino acid that is high in red meat), a substrate for Hcy, can cause skeletal muscle and growth retardation, and treatment with probiotics (PB) to mitigate skeletal muscle dysfunction. To test this, we employed cystathionine [beta]-synthase, CBS deficient mouse ([CBS.sup.+/-]) fed with/without HMD and with/without a probiotic (Lactobacillus rhamnosus) in drinking water for 16 weeks. Matrix metalloproteinase (MMP) activity, a hallmark of remodeling, was measured by zymography. Muscle functions were scored via electric stimulation. Our results suggest that compared to the wild-type, [CBS.sup.+/-] mice exhibited reduced growth phenotype. MMP-2 activity was robust in [CBS.sup.+/-] and HMD effects were successfully attenuated by PB intervention. Electrical stimulation magnitude was decreased in [CBS.sup.+/-] and CBS+/treated with HMD. Interestingly; PB mitigated skeletal muscle growth retardation and atrophy. Collectively, results imply that individuals with mild/moderate HHcy seem more prone to skeletal muscle injury and its dysfunction. Key words: dysbiosis, phosphatidylethanolamine N-methyltransferase, trimethylamine oxide, 1-carbon metabolism, cystathionine [beta]-synthase. La methylation de l'ADN epigenetique (metabolisme du carbone 1) est cruciale pour obtenir l'empreinte et le << offprinting >> genetiques, qui assurent la memoire epigenetique, et produit aussi sans equivoque une importante quantite d'homocysteine (Hcy). C'est la raison pour laquelle on recommande aux femmes enceintes de prendre de l'acide folique en prevention d'anomalies congenitales liees a une augmentation des taux d'Hcy (c.-a-d., a l'hyperhomocysteinemie (Hhcy)). Comme on le sait, les enfants nes avec une HHcy presentent plusieurs anomalies musculosquelettiques, y compris un retard de croissance. Ici, nous nous centrons sur le ou les roles du microbiome dysbiotique de l'intestin que l'on croit etre l'instigateur du << metabolisme du carbone 1 >> et de l'HHcy menant a un retard de croissance avec anomalies musculosquelettiques. Nous mettons a l'epreuve notre hypothese selon laquelle un regime alimentaire a haute teneur en methionine (RHM) (un acide amine dont les concentrations sont elevees dans la viande rouge) comme substrat de l'Hcy peut causer un retard de croissance et de formation du muscle squelettique, et l'administration de probiotiques (PB) peut attenuer le dysfonctionnement du muscle squelettique. Nous nous y sommes employes a l'aide de souris deficientes en cystathionine beta synthase ([CBS.sup.+/-]) auxquelles etait administre un RHM ou non, et avec ou sans probiotiques (Lactobacillus rhamnosus) dans l'eau de consommation pendant 16 semaines. Nous avons mesure l'activite des metalloproteinases matricielles (MMP), un element essentiel du remodelage, a l'aide de la zymographie. Nous avons note le fonctionnement des muscles a l'aide de la stimulation electrique. Nos resultats laissent entrevoir que les souris [CBS.sup.+/-] auraient presente un phenotype de croissance moins marque que les souris de type sauvage. L'activite de la MMP-2 etait robuste chez les souris [CBS.sup.+/-] et nous parvenions a attenuer les effets de l'administration d'un RHM a l'aide de PB. L'amplitude de la stimulation electrique diminuait chez les souris [CBS.sup.+/-] comme chez les souris [CBS.sup.+/-] auxquelles etait administre un RHM. Il est interessant de noter que les PB permettaient d'attenuer le retard de croissance et l'atrophie du muscle squelettique. Collectivement, les resultats laissent entendre que des sujets presentant une HHcy legere ou moderee sembleraient plus susceptibles de presenter des lesions des muscles squelettiques, ainsi que leur dysfonctionnement. [Traduit par la Redaction] Mots-cles : dysbiose, phosphatidylethanolamine N-methyltransferase, oxyde de trimethylamine, metabolisme du carbone 1, cystathionine [beta]-synthase., Introduction Although deaths from cardiovascular diseases are declining, the number of risk factors such as cholesterol, sugar, insulin, and oxidative stress are not changing significantly (Friedman 2013; Krzyminiewski et al. [...]

Background/objective Knowing the distribution of lean soft tissue (LST) among the body segments is of relevance for optimizing athletic performance, monitoring response to training, and for evaluating injury risk. Bioelectrical impedance (BIA) is a portable, low cost, and easy technique to assess body composition. However, most equations used by BIA to predict LST are not specific for the athlete population. The aim of this investigation was to develop and validate equations to estimate dual-energy X-ray absorptiometry (DXA) appendicular LST of the arms and legs based on whole-body BIA in athletes. Methods Arms and legs LST were assessed by DXA and whole-body reactance (Xc) and resistance (R) were measured by BIA in athletes from various sports. Using measures of height, the resistance index (RI) (RI = height.sup.2/R) was calculated. Prediction equations were established using a cross-validation method where 177 athletes (2/3 of sample) were used for equation development and the remaining 88 athletes (1/3 of sample) were used for equation validation. Results The developed prediction equations were as follows: arm LST = 0.940 × sex (0 = male; 1 = female) + 0.042 × total body weight (kg) + 0.080 × RI + 0.024 × Xc - 3.927; leg LST = 1.983 × sex (0 = male; 1 = female) + 0.154 × total body weight (kg) + 0.127 × RI - 1.147. Both equations validated well for the arms (mean difference = 0.11 kg, R.sup.2 = 0.89, pure error (PE) = 0.61) and for the legs (mean difference = 0.05 kg, R.sup.2 = 0.81, PE = 1.93 kg). There were no differences (p > 0.05) in the mean observed and predicted LST for the arms and legs. Conclusion The developed BIA-based prediction equations provide a valid estimation of upper and lower body LST in athletes., Author(s): Luís B. Sardinha [sup.1] , Inês R. Correia [sup.1] , João P. Magalhães [sup.1] , Pedro B. Júdice [sup.1] , Analiza M. Silva [sup.1] , Megan Hetherington-Rauth [sup.1] Author [...]

Objective Nutritional disorders cause secondary osteoporosis as well as musculoskeletal metabolism dysfunction. The Christian Orthodox Church's fasting in Mediterranean countries such Greece and Cyprus, or M.C.O.C. diet consists of self-restraint from food and/or food categories for 180 [plus or minus] 19 days of total, especially of animal protein and dairy products. This case-control study attempts to investigate the effect of this fasting pattern on musculoskeletal metabolism and bone density. Design One hundred fasters (or M.C.O.C. diet followers; 68 women and 32 men, mean 59 [plus or minus] 6.5) with 32 years average fasting time and 100 non-fasters (66 females and 34 males, mean 58.1 [plus or minus] 6.8; the control group of Mediterranean diet followers) over the age of 50, including menopausal women, were interviewed, as well as physically and laboratory examined along with DEXA measurements of the L2-4 vertebrae and hips. Nutrition data gathered through a 3-day food record during a non-fasting period, while energy intakes calculated on a daily food consumption basis. Results Given the overall low incidence of osteoporosis in the Mediterranean diet, it appears to be more than three times higher than that of M.C.O.C. diet despite the periodic restriction of food intake of animal origin into a slightly hypothermic pattern, which in turn is characterized by increased consumption of multicolored vegetable foods. Conclusions Abstinence from dairy products and meat does not adversely affect musculoskeletal metabolism or bone density. M.C.O.C. diet seems to be 'healthy' eating habit for the musculoskeletal system, as future studies expected to confirm., Author(s): Nikolaos E. Rodopaios [sup.1] , George E. Manolarakis [sup.1] , Alexandra-Aikaterini Koulouri [sup.1] , Eleni Vasara [sup.2] , Sousana K. Papadopoulou [sup.3] , Petros Skepastianos [sup.4] , Emmanouil Dermitzakis [...]