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Anabolic resistance

Michaël R Laurent
An overview of selected papers related to bone published in 2017 is provided. PURPOSE: This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year. METHODS: A PubMed search using the keyword "bone" and articles published in 2017. RESULTS: Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation...
March 15, 2018: Archives of Osteoporosis
Hussain N Alhamami, Md Main Uddin, A S M Hasan Mahmood, Karen P Briski
The hypothalamic energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK), an important regulator of counter-regulatory responses to hypoglycemia, responds to pharmacological manipulation of hindbrain AMPK activity. Dorsomedial hindbrain A2 noradrenergic neurons express hypoglycemia-sensitive metabolo-sensory biomarkers, including AMPK. Here, adult male rats were pretreated by intra-caudal fourth ventricular administration of the selective neurotoxin 6-hydroxydopamine (6-OHDA) to determine if catecholamine signaling from the aforesaid site governs hypothalamic AMPK activation during insulin-induced hypoglycemia (IIH)...
March 10, 2018: Neuroscience
Liam Bagley, Nasser Al-Shanti, Steven Bradburn, Osamah Baig, Mark Slevin, Jamie S McPhee
BACKGROUND: Regular sprint interval training (SIT) improves whole-body aerobic capacity and muscle oxidative potential, but very little is known about knee extensor anabolic or fatigue resistance adaptations, or whether effects are similar for males and females. The purpose of this study was to compare sex-related differences in knee extensor size, torque-velocity relationship and fatigability adaptations to 12 weeks SIT. METHODS: Sixteen males and fifteen females (mean (SEM) age: 41 (±2...
March 12, 2018: Journal of Strength and Conditioning Research
J Cai, W Li, T Sun, X Li, E Luo, D Jing
The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking...
March 9, 2018: Osteoporosis International
Yujie Li, Sandra Finkbeiner, Athina Ganner, Julia Gerber, Marinella Klein, Manuel Grafe, Jakob Kandzia, Antje Thien, Kathrin Thedieck, Gerhard Breves, Thomas Jank, Ralf Baumeister, Gerd Walz, Elke Neumann-Haefelin
The mechanistic target of rapamycin (mTOR) kinase is central to metabolism and growth, and has a conserved role in aging. mTOR functions in two complexes, mTORC1 and mTORC2. In diverse eukaryotes, inhibition of mTORC1 signaling increases lifespan. mTORC1 transduces anabolic signals to stimulate protein synthesis and inhibits autophagy. In this study, we demonstrate that CGEF-1, the C. elegans homolog of the human guanine nucleotide exchange factor Dbl, is a novel binding partner of RHEB-1 and activator of mTORC1 signaling in C...
February 9, 2018: Oncotarget
Takayoshi Sasako, Kohjiro Ueki
Among the tissues involved in the motor system, skeletal muscle plays an important role in systemic metabolism and is the largest organ in terms of glucose uptake. Insulin promotes anabolism of nutrients in skeletal muscle, as in other insulin-targeted organs, and maintains muscle volume, in cooperation with insulin-like growth factor-1. In humans, along with aging, insulin resistance is induced in skeletal muscle, which could lead to systemic insulin resistance, and circulating IGF-1 levels are lowered. These changes contribute to the development of sarcopenia, in which function and volume of skeletal muscle are impaired, and modulation of the insulin/IGF-1 signaling could be promising in treatment of sarcopenia...
2018: Clinical Calcium
S Antoun, B Raynard
In the field of oncology, it is well recognized that a decrease in mass, density, strength, or function of skeletal muscle is associated to increased treatment toxicities and postoperative complications, as well as poor progression-free survival and overall survival. The ability of amino acids to stimulate protein synthesis in cancer patients is reduced. Considering nutritional intervention, this anabolic resistance could be in a part counteracted by increasing protein or by giving specific amino acids. In particular, Leucine might counteract this anabolic resistance not only by increasing substrate availability, but also by directly modulating the anabolic signal pathway...
February 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Olivier L Mantha, Sergio Polakof, Jean-François Huneau, François Mariotti, Nathalie Poupin, Daniel Zalko, Helene Fouillet
Little is known about how diet-induced obesity and insulin resistance affect protein and amino acid (AA) metabolism in tissues. The natural relative abundances of the heavy stable isotopes of C (δ 13C) and N (δ 15N) in tissue proteins offer novel and promising biomarkers of AA metabolism. They, respectively, reflect the use of dietary macronutrients for tissue AA synthesis and the relative metabolic use of tissue AA for oxidation v. protein synthesis. In this study, δ 13C and δ 15N were measured in the proteins of various tissues in young adult rats exposed perinatally and/or fed after weaning with a normal- or a high-fat (HF) diet, the aim being to characterise HF-induced tissue-specific changes in AA metabolism...
March 5, 2018: British Journal of Nutrition
Brad Jon Schoenfeld, Alan Albert Aragon
Controversy exists about the maximum amount of protein that can be utilized for lean tissue-building purposes in a single meal for those involved in regimented resistance training. It has been proposed that muscle protein synthesis is maximized in young adults with an intake of ~ 20-25 g of a high-quality protein; anything above this amount is believed to be oxidized for energy or transaminated to form urea and other organic acids. However, these findings are specific to the provision of fast-digesting proteins without the addition of other macronutrients...
2018: Journal of the International Society of Sports Nutrition
Hui Chang, Shanfeng Jiang, Xiufeng Ma, Xin Peng, Jie Zhang, Zhe Wang, Shenhui Xu, Huiping Wang, Yunfang Gao
Previous hibernation studies demonstrated that such a natural model of skeletal muscle disuse causes limited muscle atrophy and a significant fast-to-slow fiber type shift. However, the underlying mechanism as defined in a large-scale analysis remains unclarified. Isobaric tags for relative and absolute quantification (iTRAQ) based quantitative analysis were used to examine proteomic changes in the fast extensor digitorum longus muscles (EDL) of Daurian ground squirrels (Spermophilus dauricus). Although the wet weights and fiber cross-sectional area of the EDL muscle showed no significant decrease, the percentage of slow type fiber was 61% greater (P < 0...
February 13, 2018: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Fanxing Zeng, Hua Zhao, Jingwen Liao
This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR) signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT) implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70S6K ), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle...
December 2017: Biology of Sport
Søren Reitelseder, Kasper Dideriksen, Jakob Agergaard, Nikolaj M Malmgaard-Clausen, Rasmus L Bechshoeft, Rasmus K Petersen, Anja Serena, Ulla R Mikkelsen, Lars Holm
PURPOSE: The responsiveness of older individuals' skeletal muscle to anabolic strategies may be impaired. However, direct comparisons within the same experimental setting are sparse. The aim of this study was to assess the resting and post-resistance exercise muscle protein synthesis rates in response to two types of milk protein and carbohydrate using a unilateral exercise leg model. METHODS: Twenty-seven older (69 ± 1 year, mean ± SE) men were randomly assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or carbohydrate (CHO)...
February 22, 2018: European Journal of Nutrition
Robert W Davies, Brian P Carson, Philip M Jakeman
Whey protein (WP) is a widely consumed nutritional supplement, known to enhance strength and muscle mass during resistance training (RT) regimens. Muscle protein anabolism is acutely elevated following RT, which is further enhanced by WP. As a result, there is reason to suggest that WP supplementation may be an effective nutritional strategy for restoring the acute loss of contractile function that occurs following strenuous RT. This systematic review and meta-analysis provides a synthesis of the literature to date, investigating the effect of WP supplementation on the recovery of contractile function in young, healthy adults...
February 16, 2018: Nutrients
Robert Howlett, Nicholas Read, Anpu Varghese, Charles Kershaw, Y Hancock, Margaret C M Smith
Polyprenol phosphate mannose (PPM) is a lipid-linked sugar donor used by extra-cytoplasmic glycosyl tranferases in bacteria. PPM is synthesiszed by polyprenol phosphate mannose synthase, Ppm1, and in most Actinobacteria is used as the sugar donor for protein O-mannosyl transferase, Pmt, in protein glycosylation. Ppm1 and Pmt have homologues in yeasts and humans, where they are required for protein O-mannosylation. Actinobacteria also use PPM for lipoglycan biosynthesis. Here we show that ppm1 mutants of Streptomyces coelicolor have increased susceptibility to a number of antibiotics that target cell wall biosynthesis...
February 1, 2018: Microbiology
Tora S Solheim, Barry J A Laird, Trude R Balstad, Asta Bye, Guro Stene, Vickie Baracos, Florian Strasser, Gareth Griffiths, Matthew Maddocks, Marie Fallon, Stein Kaasa, Kenneth Fearon
Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment...
February 9, 2018: BMJ Supportive & Palliative Care
D Goltzman
Vitamin D, synthesized in the skin or absorbed from the diet, undergoes multi-step enzymatic conversion to its active form, 1,25-dihydroxy vitamin D [1,25(OH)2 D], followed by interaction with the vitamin D receptor (VDR), to modulate target gene expression. Loss-of function mutations in the genes encoding the enzymes regulating these processes, or in the VDR, result in human diseases, which have demonstrated the paramount role of 1,25(OH)2 D in mineral and skeletal homeostasis. Mouse genetics has been used to create disease phenocopies which have produced considerable insight into the mechanisms of 1,25(OH)2 D regulation of mineral and skeletal metabolism...
February 12, 2018: Histochemistry and Cell Biology
Claudio Nieto Jimenez, Jorge Cajigal Vargas, Vjera Sofia Triantafilo Vladilo, Jose Naranjo Orellana
Introduction: The Chilean Army considers processes that can optimize physical capacities for responding to the impact of situations and given stressors. The study of the effect of hypothermia as a stressor agent (HSA) and its relationship with cardiovascular, hematological, anthropometric, endocrine, and immunological parameters has not been fully addressed experimentally in military populations. Objective: To identify the endocrine, hematological, cardiovascular, and immunological changes caused by HSA and to associate these variables with body composition and physical fitness in the military special operation courses of the Chilean Army...
February 7, 2018: Military Medicine
Barbara Strasser, Konstantinos Volaklis, Dietmar Fuchs, Martin Burtscher
Muscle atrophy is an unfortunate effect of aging and many diseases and can compromise physical function and impair vital metabolic processes. Low levels of muscular fitness together with insufficient dietary intake are major risk factors for illness and mortality from all causes. Ultimately, muscle wasting contributes significantly to weakness, disability, increased hospitalization, immobility, and loss of independence. However, the extent of muscle wasting differs greatly between individuals due to differences in the aging process per se as well as physical activity levels...
February 2018: Aging and Disease
Robert W Morton, Daniel A Traylor, Peter J M Weijs, Stuart M Phillips
PURPOSE OF REVIEW: Skeletal muscle mass with aging, during critical care, and following critical care is a determinant of quality of life and survival. In this review, we discuss the mechanisms that underpin skeletal muscle atrophy and recommendations to offset skeletal muscle atrophy with aging and during, as well as following, critical care. RECENT FINDINGS: Anabolic resistance is responsible, in part, for skeletal muscle atrophy with aging, muscle disuse, and during disease states...
April 2018: Current Opinion in Critical Care
Cameron J Mitchell, Randall F D'Souza, Vandre Casagrande Figueiredo, Alex Chan, Kirsten M Aasen, Brenan Durainayagam, Sarah M Mitchell, Andrew J Sinclair, Ingrid Marie Egner, Truls Raastad, David Cameron-Smith, James F Markworth
Arachidonic acid (ARA), a polyunsaturated ω-6 fatty acid, acts as precursor to a number of prostaglandins with potential roles in muscle anabolism. It was hypothesized that ARA supplementation might enhance the early anabolic response to resistance exercise (RE) by increasing muscle protein synthesis (MPS) via mammalian target of rapamycin (mTOR) pathway activation, and/or the late anabolic response by modulating ribosome biogenesis and satellite cell expansion. Nineteen men with {greater than or equal to}1 year of resistance training experience were randomized to consume either 1...
February 1, 2018: Journal of Applied Physiology
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