Glutamine and tissue repair -
This product is not intended to diagnose, treat, cure, or prevent any disease. L-Glutamine mg Need this product? We can help. Overview Your Better Choice for Professional-Grade Supplements L-Glutamine is the most abundant amino acid in the body.
Quantity: Tablets Click to View the Product Data Sheet. Bulk Request Form ×. Product Information. Yes No. Among the 20 amino acids detailed in the genetic code, glutamine is one of the most versatile for amino acid metabolism and immune function.
The biologically important form is L-glutamine. But for surgery healing, or times of stress or trauma, when we cannot meet the greater demands, then we must ingest it. Rachelle Herdman, Custom Health Guide.
Glutamine is a key molecule in new tissue formation, repair of injuries, and energy production, and it contributes to many critical biochemical reactions.
It also supports good blood circulation for optimal wound healing. After injury, the body cannot produce optimal amounts of glutamine, therefore supplementing can be beneficial for recovery and immune health. There is a robust body of evidence supporting the association between L-glutamine supplementation, and improved injury and wound healing.
There are modest amounts of glutamine in a well-balanced diet that contains a variety of vegetables, nuts, and lean sources of protein, usually enough to meet the nutritional needs of an average sedentary or mildly active person.
For example, a serving of egg, tofu or beef can provide about mg. But surgery recovery puts greater demands on body systems, creating increased L-glutamine needs that cannot be met through diet alone.
Cooking can also destroy glutamine in certain foods, especially vegetables. L-glutamine is commonly stored in muscles and released into the bloodstream during times of physical stress.
In health and disease, the consumption of glutamine by immune cells is similar or greater than glucose. Lymphocytes, neutrophils, and macrophages utilize glutamine at especially high rates under catabolic conditions, such as recovery from wounds or surgery.
Glutamine is considered anabolic for skeletal muscle, meaning that it encourages muscle to repair and build up. It plays essential roles in pH regulation, maintaining a healthy alkaline-acid balance, and in gluconeogenesis, providing a steady glucose supply to healing tissues.
There is evidence that elevated adrenal hormones including cortisol deplete glutamine reserves, and that glutamine supplementation boosts tissue repair. In addition, it provides fuel for immune and intestinal cells and helps keep the cell-to-cell connections in the intestines strong.
Many researchers have found that glutamine can enhance heat shock protein production under stress and improve cell survival after injury. Research results confirm the use of glutamine to enhance heat shock proteins before a serious clinical stress such as major surgical procedures e.
cardiac, vascular, and transplantation or at the start of critical illness. Depletion of glutamine has been associated with increased risk of post-operative complications, including infections, organ failure, and death.
Deficiency of L-glutamine is linked with inflammation, oxidative stress, and interruptions in immune system functioning, as well as reduced stamina and poor tissue repair. A review collected data on how physiological stress can affect cortisol and immune cell functions.
The consequences include transient inflammation of joints or connective tissues; elevation of inflammatory mediators; increases of free radicals that cause oxidative stress; and a higher risk of infections or autoimmune disease. Researchers noted that these effects can be mitigated by L-glutamine.
Studies since confirm that wound healing requires energy, protein, L-glutamine and other key amino acids including arginine, as well as a variety of vitamins and trace elements. With our aging population, surgical wound repair research has been significant in recent years—especially studies addressing glutamine supplementation.
From studies performed in vitro and in vivo , it is well known that glutamine is a crucial nutrient for wound healing. Research in found that glutamine supplementation to patients for 6 days before and 5 days after undergoing colorectal surgery significantly reduced the incidence of wound complications.
A study confirmed that for trauma patients suffering from poor wound healing, supplementation of glutamine, in combination with antioxidant nutrients, sped up wound closure compared with patients who received placebo.
Additionally, the patients who received glutamine had better tissue oxygen levels and increased oxygen saturation, compared to the placebo group.
Patients recovering from severe burns have better wound healing with glutamine supplementation. Two important trials found that the rate of wound healing was higher in patients receiving glutamine, compared with controls.
A meta-analysis of several randomized controlled trials published in in the Journal of Parenteral and Enteral Nutrition , evaluated the benefits of glutamine for surgical patients receiving parenteral nourishment.
The glutamine-supplemented patients had shorter hospital stays, reduced by 4 to 5 days. They also experienced a significant decrease in infections and post-operative complications. In our clinic, our patients recovering from surgery who start L-glutamine pre-operatively and continue for 4 weeks after their procedures report faster wound healing.
They also notice fewer gastrointestinal symptoms after anesthetics, a lower incidence of infections, good immune function, and feeling more confidence in their healing process with less anxiety than they had anticipated. Recommendation: L-glutamine 1, to 2,mg daily total, with any meals, from a vegan source, or as directed by your healthcare provider.
Surgery Recovery L-Glutamine Megabite Design T For SURGERY RECOVERY , L-glutamine stimulates wound healing and the formation of new protein, slows breakdown of tissue proteins, and is an energy fuel for muscle cell division.
What is L-glutamine? How does L-glutamine work in the body? How L-glutamine improves surgery recovery L-glutamine enhances wound repair in the following ways: After injury or surgical incisions, glutamine is rapidly released from muscle stores to provide fuel to tissues that are healing.
Glutamine is essential for healthy immune responses and inflammatory activity. It promotes the proper function, proliferation, and survival of immunity cells; and the gene expression of immune system cells depends upon glutamine availability. Glutamine plays a prominent role in the initiation and progression of the inflammatory response.
Glutamine Restorative care a key role in tizsue essential metabolic Glutamine and tissue repair and wnd an important modulator of the heat Glutamine and tissue repair protein HSP response, a crucial mechanism to tossue cellular homeostasis Glutamine and tissue repair to promote cell resistance to injury rrepair Glutamine and tissue repair. This review summarized Glytamine effects of Nutritional needs l -glutamine or Goutamine dipeptide l -alanyl- l -glutamine upon muscle injury and inflammation, as well as muscle recovery from resistance training. The kDa HSP HSP70 expression is enhanced by glutamine, via the hexosamine biosynthetic pathway, which inhibits the NF-κB pathway regenerating and recovering myofibers through the regulation of the early inflammatory response to muscle injury, which may be impaired by local and systemic inflammatory injury due to reduced intracellular levels of HSP Studies show that chronic oral administration of free l -glutamine or the dipeptide can attenuate the injury and inflammation induced by intense aerobic and exhaustive exercise. However, the effects on muscle recovery from resistance training are unclear.Thank you tisssue visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend Glutamime use a more up to tissuee browser tepair turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without Enhancing intestinal transit and Repaor.
Muscle regeneration is sustained by infiltrating macrophages and the consequent Roasted broccoli dishes of satellite repir 1234. Macrophages and satellite reoair communicate in different ways 1 tiesue, 23 snd, 45tlssue their metabolic interplay has not Glutamine and tissue repair investigated.
Tisaue we show, in a mouse model, that muscle injuries Restorative care Glutamind are characterized by intra-tissue restrictions of glutamine.
Low levels of glutamine endow macrophages with the repai ability Cholesterol level guidelines secrete glutamine via enhanced glutamine synthetase GS activity, at the expense of glutamine oxidation re;air by glutamate dehydrogenase 1 GLUD1.
Glud1 -knockout macrophages display constitutively high GS znd, which prevents glutamine Repqir. The uptake of macrophage-derived glutamine by satellite cells through Healthy Carbohydrate Sources glutamine transporter Blood circulation in hands activates mTOR and repwir the proliferation and ans of satellite cells.
Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves muscle regeneration and functional recovery in response to acute injury, ischaemia andd ageing. Tisseu, SLC1A5 blockade in Glutamine and tissue repair cells or Anr inactivation in macrophages negatively affects satellite cell functions and muscle Glutamine and tissue repair.
These results highlight the metabolic crosstalk between Gluhamine cells and macrophages, in which macrophage-derived Ginseng farming techniques sustains the GGlutamine of satellite Gltuamine. Thus, the targeting of GLUD1 may offer therapeutic opportunities Glutamine and tissue repair the regeneration of injured or aged muscles.
This is a preview of subscription content, access via your institution. RNA sequencing data have been deposited in the Gene Expression Omnibus GEO data repository, with accession number GSE Other data that support the findings of this study are available from the corresponding author M. upon reasonable request.
Source data are provided with this paper. Bentzinger, C. Cellular dynamics in the muscle satellite cell niche. EMBO Rep.
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Macrophages and skeletal muscle regeneration: a clodronate-containing liposome depletion study. Rennie, M. Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle—protein turnover. Metabolism 38 Suppl 147—51 Biolo, G.
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: Glutamine and tissue repair| Surgery Recovery L-Glutamine | Pacific Center for Naturopathic Medicine | Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats. Blass SC, et al: Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: a PRCT. Wang W, Choi RH, Solares GJ, et al. Acta Physiol Scand. Krause M, Heck TG, Bittencourt A, et al. Thus, oral supplementation with l -glutamine administered with l -alanine or as DIP has been shown to induce HSPmediated cytoprotective effects in response to muscle injury and inflammation [ ]. Position statement. |
| Pacific Center for Naturopathic Medicine | Perdiguero, E. Get the most important science stories of the day, free in your inbox. Download references. When we consume protein in the diet, the protein in the gastrointestinal tract is broken down into individual amino acids and then put back together again as new protein. Sandri provided critical edits to the text. Int J Sports Med. |
| Benefits of Glutamine Amino Acid Supplements | Thorne | Source data are provided with this paper. Inflammation-induced leukocyte accumulation in injured skeletal muscle: role of mast cells. Its activity is enhanced by glutamine via O-glycosylation, leading to the translocation and transcriptional stimulation of key transcription factors HSF-1 and Sp1 required for maximal HSP70 induction [ ]. The skeletal muscle amino acid metabolism generates glutamine to detoxify the ammonia produced [ 17 , 18 ]. USA , E—E Tags Vitamin D. CAS PubMed Google Scholar Nurjhan, N. |
| Search form | mTORC1 controls the adaptive transition of quiescent stem cells from G 0 to G Alert. Zhang, P. mTOR is necessary for proper satellite cell activity and skeletal muscle regeneration. Jewell, J. Differential regulation of mTORC1 by leucine and glutamine. Science , — Rayagiri, S. Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal. Sousa-Victor, P. Geriatric muscle stem cells switch reversible quiescence into senescence. Bernet, J. p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Jin, L. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth. Cancer Cell 27 , — Liu, P. α-Ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Obara, H. Acute limb ischemia. Sayer, A. New horizons in the pathogenesis, diagnosis and management of sarcopenia. Age Ageing 42 , — Vinciguerra, M. Regulation of muscle atrophy in aging and disease. Carobbio, S. Deletion of glutamate dehydrogenase in β-cells abolishes part of the insulin secretory response not required for glucose homeostasis. He, Y. Glutamine synthetase deficiency in murine astrocytes results in neonatal death. Glia 58 , — PubMed Google Scholar. Mingote, S. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice. Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin. USA , E—E LaFleur, M. A CRISPR—Cas9 delivery system for in vivo screening of genes in the immune system. Sanjana, N. Improved vectors and genome-wide libraries for CRISPR screening. Methods 11 , — Pasut, A. Isolation and culture of individual myofibers and their satellite cells from adult skeletal muscle. Casazza, A. Cancer Cell 24 , — Download references. was supported by an ERC Consolidator grant ImmunoFit , FWO-SBO ZL3C , Horizon research and innovation programme under the Marie Skłodowska-Curie grant agreement no. We thank V. van Hoef for bioinformatic analyses; S. Fendt, C. Frezza, A. Musarò, G. Cossu and J. Marine for advice; and S. Trusso Cafarello and S. Willox for technical support. and M. received long-term structural Methusalem funding by the Flemish Government; P. is supported by an ERC PoC ERC and Advanced grant EU-ERC Shang received a grant from the China Scholarship Council CSC ; E. received a grant from the FWO N. Present address: Faculty of Rehabilitation Sciences, REVAL, Hasselt University UHasselt , Diepenbeek, Belgium. Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium. Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium. Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal. Molecular Biotechnology Center, University of Torino, Turin, Italy. Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy. Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium. Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium. Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland. VIB—KU Leuven Center for Brain and Disease Research, Leuven, Belgium. Department of Neuroscience, KU Leuven, Leuven, Belgium. Centro de Investigaciones, Fundacion Cardiovascular de Colombia, Floridablanca, Colombia. Department of Health Sciences and Technology, ETH, Zurich, Switzerland. Department of Oncology, Ludwig Cancer Research, University of Lausanne, Epalinges, Switzerland. Venetian Institute of Molecular Medicine, Padua, Italy. Department of Biomedical Science, University of Padova, Padua, Italy. Department of Medicine, McGill University, Montreal, Quebec, Canada. Metabolomics Core Facility, Center for Cancer Biology, VIB, Leuven, Belgium. Metabolomics Core Facility, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium. Department of Molecular Biotechnology and Health Science, Molecular Biotechnology Centre, University of Torino, Turin, Italy. You can also search for this author in PubMed Google Scholar. Shang performed experimental design, all experiments, data acquisition and interpretation, and wrote the manuscript. and R. performed in vitro assays and histology. performed all the ligations and histological staining. performed angiogenic and in vitro assays. provided AAV vectors. performed Seahorse measurements. and P. generated GLUD1 conditional knockout mice and provided critical suggestions. provided the transgenic mice expressing Cre ERT under the Pax7 promoter, and provided critical edits to the text. Sandri provided critical edits to the text. helped in the experiments with GLS-knockout macrophages and provided Gls ΔMo mice. supported with metabolic assays and critical suggestions in manuscript writing. designed and supervised all the in vitro and in vivo gene editing approaches, and provided critical edits to the text. performed the experimental design and data analysis, conducted scientific direction and wrote the manuscript. Correspondence to Emanuele Berardi or Massimiliano Mazzone. Peer review information Nature thanks Terry Partridge and the other, anonymous, reviewer s for their contribution to the peer review of this work. a , Western blot for GLUD1 in BMDMs from control and Glud1 ΔMo mice. Vinculin was used as loading control. Representative image of three independent blots. Injured mice were CD Baseline B. Numbers represent fold change versus vinculin. A representative a — m , o — w or a pool n of at least two independent experiments is shown. Glutamine supplementation has also been shown to enhance collagen synthesis, supporting overall tissue repair and potentially cartilage health within joints. Research has also been conducted regarding the potential importance of glutamine in cancer therapy and recovery. The information can be conflicting at times as it has been noted that many cancer cells also require glutamine for their main energy source or fuel. In theory, supplementation of glutamine to recovering cancer patients could fuel the cancer progression, but research has gone both ways on this matter. Viewing glutamine as a vital nutrient for the body that can be in a negative state, dependent on the demand, it has been theorized that many larger tumors actually become glutamine traps, selfishly consuming the available glutamine and depriving the rest of the body. If this is true, then other cells of the immune system and gastrointestinal tract could become debilitated and contribute to the demise of the patient. So, the question comes is to if we provide higher levels of glutamine to those patients, could we potentially enhance overall health and strength, allowing the body to rebound and recover? Essentially, when it comes to health, recovery and overall energy production, our body needs many nutrients to function correctly and at an optimal level. Glutamine is one of many of those nutrients that can impact cellular function at the gastrointestinal, immune, neurological and skeletal muscle level. Deficiencies of glutamine may explain poor recovery and healing associated with numerous conditions while enhanced levels may be correlated with a stronger immune response, tissue healing and gastrointestinal health. Glutamine is required by every animal species to ensure optimal cellular health. The question comes as to if we or our animal companions are consuming enough or producing enough intrinsically to meet demands? In cases of injury, surgery or long term illness, especially when there is a reduced caloric intake, glutamine supplementation may prove to be essential. Considering the diet consumed by the average human and that of our animal companions, especially when taking into consideration the high levels of stress that we all endure and the health implications, glutamine supplementation may be a good thing, helping to support overall health, resistance to infection and enhanced recovery. So, how does glutamine supplementation apply to your, your pets or your equine companions? If you or them are recovering from an illness, especially if the condition is prolonged in nature, glutamine may enhance overall recovery. If you are suffering from immune dysfunction, allergies or gastrointestinal problems, glutamine supplementation may provided added benefits improving outcomes and long term management. It helps to reduce inflammation and protect your muscles from damage. It is difficult to get a large amount of HMB through food, so ask your healthcare provider if HMB supplementation may be right for you. Deutz NE, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. This section includes technical information. At this time, we are experiencing problems with broken links on our site. As an interim solution, for full site functionality you must enable functional and advertising cookies. If you continue to opt-out of these cookies, some content on our site may not be viewable. We use functional cookies to analyze your use of the site, improve performance and provide a better customer experience. We use advertising cookies to allow us, through certain data assigned and obtained from the user's device, to store or share with third parties information related to user's browsing activity in our website, in order to create an advertising profile and place relevant advertising in our website or those third parties websites. For more information about how Abbott uses cookies please see our Cookie Policy and Privacy Policy. 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Glutamine and tissue repair -
Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production.
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Download references. Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes , São Paulo, SP, , Brazil. You can also search for this author in PubMed Google Scholar.
RR and JT were responsible for all the steps of the review. The figure was drawn by RR. Both authors read and approved the final manuscript. Correspondence to Raquel Raizel. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Raizel, R. Role of glutamine, as free or dipeptide form, on muscle recovery from resistance training: a review study. Nutrire 43 , 28 Download citation. Received : 23 August Accepted : 07 November Published : 05 December Anyone you share the following link with will be able to read this content:.
Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Download PDF. Abstract Background Glutamine plays a key role in several essential metabolic processes and is an important modulator of the heat shock protein HSP response, a crucial mechanism to maintain cellular homeostasis and to promote cell resistance to injury and death.
Main body of the abstract The kDa HSP HSP70 expression is enhanced by glutamine, via the hexosamine biosynthetic pathway, which inhibits the NF-κB pathway regenerating and recovering myofibers through the regulation of the early inflammatory response to muscle injury, which may be impaired by local and systemic inflammatory injury due to reduced intracellular levels of HSP Zhang, P.
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Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice. Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin.
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Improved vectors and genome-wide libraries for CRISPR screening. Methods 11 , — Pasut, A. Isolation and culture of individual myofibers and their satellite cells from adult skeletal muscle.
Casazza, A. Cancer Cell 24 , — Download references. was supported by an ERC Consolidator grant ImmunoFit , FWO-SBO ZL3C , Horizon research and innovation programme under the Marie Skłodowska-Curie grant agreement no.
We thank V. van Hoef for bioinformatic analyses; S. Fendt, C. Frezza, A. Musarò, G. Cossu and J. Marine for advice; and S. Trusso Cafarello and S. Willox for technical support. and M. received long-term structural Methusalem funding by the Flemish Government; P.
is supported by an ERC PoC ERC and Advanced grant EU-ERC Shang received a grant from the China Scholarship Council CSC ; E. received a grant from the FWO N. Present address: Faculty of Rehabilitation Sciences, REVAL, Hasselt University UHasselt , Diepenbeek, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium. Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal. Molecular Biotechnology Center, University of Torino, Turin, Italy.
Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy. Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium. Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland. VIB—KU Leuven Center for Brain and Disease Research, Leuven, Belgium.
Department of Neuroscience, KU Leuven, Leuven, Belgium. Centro de Investigaciones, Fundacion Cardiovascular de Colombia, Floridablanca, Colombia. Department of Health Sciences and Technology, ETH, Zurich, Switzerland.
Department of Oncology, Ludwig Cancer Research, University of Lausanne, Epalinges, Switzerland. Venetian Institute of Molecular Medicine, Padua, Italy. Department of Biomedical Science, University of Padova, Padua, Italy.
Department of Medicine, McGill University, Montreal, Quebec, Canada. Metabolomics Core Facility, Center for Cancer Biology, VIB, Leuven, Belgium. Metabolomics Core Facility, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
Department of Molecular Biotechnology and Health Science, Molecular Biotechnology Centre, University of Torino, Turin, Italy. You can also search for this author in PubMed Google Scholar.
Shang performed experimental design, all experiments, data acquisition and interpretation, and wrote the manuscript. and R. performed in vitro assays and histology. performed all the ligations and histological staining. performed angiogenic and in vitro assays.
provided AAV vectors. performed Seahorse measurements. and P. generated GLUD1 conditional knockout mice and provided critical suggestions. provided the transgenic mice expressing Cre ERT under the Pax7 promoter, and provided critical edits to the text.
Sandri provided critical edits to the text. helped in the experiments with GLS-knockout macrophages and provided Gls ΔMo mice. supported with metabolic assays and critical suggestions in manuscript writing.
designed and supervised all the in vitro and in vivo gene editing approaches, and provided critical edits to the text. performed the experimental design and data analysis, conducted scientific direction and wrote the manuscript.
Correspondence to Emanuele Berardi or Massimiliano Mazzone. Peer review information Nature thanks Terry Partridge and the other, anonymous, reviewer s for their contribution to the peer review of this work.
a , Western blot for GLUD1 in BMDMs from control and Glud1 ΔMo mice. Vinculin was used as loading control. Representative image of three independent blots. Injured mice were CD Baseline B. Numbers represent fold change versus vinculin. A representative a — m , o — w or a pool n of at least two independent experiments is shown.
Scale bars, 50 μm. Graphs show mean ± s. Source data. In a — c , experiments show representative values of two independent experiments; d , e show values from one single experiment.
i , Quantification of macrophage phagocytosis. j , k , Quantification j , and representative images k , of total endothelial sprout length of spheroid containing HUVECs and wild-type or Glud1 ΔMo BMDMs. All experiments show representative values of at least two independent experiments.
o , Quantification of satellite cells on tibialis anterior muscles 1 day post-CTX injury, stained for pHH3 and PAX7. u , v , Evaluation of the conversion of GLUD1 activity u , and GS activity v , in muscle-infiltrating macrophages, sorted 1 day post-CTX.
One unit for the conversion of glutamate to 2-OG is the amount of enzyme that will generate 1 μmole of NADH per minute at pH 7. The control condition in u , v is the same one displayed in Fig.
All experiments except for o show representative values of at least two independent experiments, o shows values from one single experiment.
c , RT—qPCR of Slc1a5 knockdown efficiency in C2C12 cells. d , [U- 14 C]glutamine uptake in SLC1A5-deficient C2C12 cells SLC1A5 KD generated by co-expressing Cas9 along with a gRNA targeting the Slc1a5 locus. Parental cells control and cells transduced with a nontargeting control gRNA were used as negative controls.
g , RT—qPCR analysis of the proliferation marker Pcna in control or SLC1A5-KD C2C12 cells, or control C2C12 treated with the mTOR inhibitor Torin2, cultured for 18 h in BMDM-conditioned glutamine-reduced growth medium, in which the only glutamine present comes from wild-type or GLUD1-knockout BMDMs.
h , RT—qPCR analysis of the differentiation marker Myog in control or SLC1A5-KD C2C12 cells, or control C2C12 treated with the mTOR inhibitor Torin2, cultured for 72 h in BMDM-conditioned glutamine-reduced differentiation medium, in which the only glutamine present comes from wild-type or GLUD1-knockout BMDMs.
i , Representative images of an immunofluorescence for PAX7 on a pure satellite cell population, freshly isolated from hindlimb muscles of wild-type mice. j , RT—qPCR for Slc1a5 in satellite cells, transduced with the same lentivirus as above.
The graph shows values of three biological repetitions per condition. k , l , Quantification k and representative images l of EdU by immunofluorescence in control or SLC1A5-KD satellite cells. m — o , Quantification m , n and representative images o of fusion index and myotube size in control or SLC1A5-KD satellite cells after 5 days of culture in differentiation medium.
A nontargeting control gRNA was used as a control. a , Schematic of the AAV8 expression vector for in vivo targeting of satellite cells. U6, Pol III promoter driving the expression of the gRNA targeting the Slc1a5 locus or a nontargeting control gRNA.
b , Schematic of an AAV8-based CRISPR—Cas9-mediated in vivo genome editing. Nontargeting control gRNA was used as a control. Scale bars, 50 μm c , 20 μm h. In a — d , representative values of two independent experiments are shown; e , f show values of one experiment.
Scale bars, 20 μm. In a — i , representative values of at least two independent experiments are shown; j — n show values of one experiment. c , d , 2-OG-to-succinate ratio in wild-type or GLS-knockout BMDMs c and 2-OG-to-succinate ratio in wild-type or GLUD1-knockout BMDMs d.
n — q , RT—qPCR of Tnfa n , Cxcl9 o , Mrc1 p and Retnla q in BMDMs isolated from control and Gls ΔMo mice. r , Scheme illustrating the physiological role of GLUD1 in macrophages in response to muscle damage.
During muscle disruption, ischaemia or ageing, interstitial glutamine drops—probably because of the loss in myofibres a major glutamine source and poor blood supply. Infiltrating macrophages respond to glutamine starvation by reducing their oxidative GLUD1 activity in favour of GS activity.
Macrophage-derived glutamine is released and progressively fills the muscle interstitium, where it is taken up by satellite cells, promoting their proliferation and differentiation into new fibres two processes that are favoured by glutamine-dependent mTOR activation. Towards the end of this regenerative process, the newly generated fibres will undertake glutamine production and inflammation will be progressively resolved.
GLUD1-deficient macrophages are metabolically pre-adapted towards glutamine synthesis and release, thus preventing this glutamine drop. It follows that—in the case of muscle damage—macrophage-specific knockout of Glud1 or pharmacological GLUD1 blockade strengthens satellite cell activation, ultimately leading to therapeutic muscle regeneration.
Supplementary Figure 1 Uncropped western blot scans. The figure shows the original, uncropped scans of the western blot images displayed in Fig.
Reprints and permissions. Shang, M. Macrophage-derived glutamine boosts satellite cells and muscle regeneration. Download citation. Received : 01 February Accepted : 05 August Published : 28 October Issue Date : 26 November Anyone you share the following link with will be able to read this content:.
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