scholarly journals Effects of Glycine Supplementation on Mitochondrial Function and Protein Degradation in Skeletal Muscle of Old Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1010-1010
Author(s):  
Giulia Lizzo ◽  
Kamila Muller ◽  
Jonathan Thevenet ◽  
Stefan Christen ◽  
Kim Zarse ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Mitochondrial Function ◽  
Rna Seq ◽  
Cross Sectional ◽  
Ammonia Metabolism ◽  
Cellular Processes ◽  
Young Subjects ◽  
The Impact ◽  
Old Mice

Abstract Glycine is the simplest amino acid and it has a pivotal role in different metabolic processes, such as being a building block of glutathione, collagen and purine bases, or taking part in methylation reactions, detoxication and ammonia metabolism. Although considered for many years a non-essential amino acid, glycine levels are decreased in certain conditions, as the endogenous synthesis cannot fulfill the needs required to sustain all the cellular processes in which glycine is involved. Here we describe that glycine levels are significantly lower in skeletal muscle of aged zebrafish and mice and in plasma of humans compared to young subjects. We therefore fed healthy old mice for 6 weeks with a glycine-supplemented diet and observed a significant restoration of glycine levels in skeletal muscle and liver towards young mouse levels. Moreover, old mice showed decreased mitochondrial function in glycolytic and oxidative fibers, and a significant increase in oxygen consumption was observed in glycolytic fibers after glycine supplementation. The improvement of mitochondrial function is not associated to an increased mitochondrial biogenesis or an increased antioxidant capacity, but glycine supplementation increases both total GSH and GSSG levels, suggestive of a pro-oxidant environment. Overall, glycine supplementation induced an increase in the cross-sectional area of fibers. Finally, we carried out RNA-Seq study to decipher the impact of higher glycine intake. Our results suggest that age-associated glycine deficiency plays an important role in atrophy of muscle, especially in glycolytic fibers, and is reversible with a dietary supplementation.

scholarly journals Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease

2017 ◽  
Vol 131 (15) ◽  
pp. 1919-1922 ◽  
Author(s):  
Gareth A. Nye ◽  
Giorgos K. Sakellariou ◽  
Hans Degens ◽  
Adam P. Lightfoot
Keyword(s):  
Skeletal Muscle ◽  
Sexual Dimorphism ◽  
Mitochondrial Function ◽  
Recent Article ◽  
Cellular Processes ◽  
Wide Range ◽  
Health And Disease ◽  
Muscle Health ◽  
The Impact

Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies. However, the impact of sexual dimorphism in this context is less clear, with several studies reporting conflicting observations. For instance in ageing studies, a rodent model reported female muscles have higher antioxidant capacity compared with males; in contrast, human studies demonstrate no sex difference in mitochondrial bioenergetics and oxidative damage. These divergent observations highlight the importance of considering models and methods used to examine mitochondrial function, when interpreting these data. The use of either isolated or intact mitochondrial preparations in many studies appears likely to be a source of discord, when comparing many studies. Overall, it is now clear that more research is needed to determine if sexual dimorphism is a contributing factor in the development of myopathologies.

scholarly journals Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Rasmus J. O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Amino Acid ◽  
Glucose Homeostasis ◽  
Gene Set ◽  
Branched Chain Amino Acid ◽  
Human Myotubes ◽  
Branched Chain ◽  
The Impact

Abstract Aims/hypothesis Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified. Methods Plasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific Ppargc1a knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and quantitative RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PPARGC1A and ESRRA in the expression of the BCAA gene set. Radiolabelled leucine was used to analyse the impact of oestrogen-related receptor α (ERRα) knockdown on leucine oxidation. Results Impairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37–56% after an OGTT in the NGT group, whereas no changes were detected in individuals with type 2 diabetes. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of branched-chain amino acid transaminase 2, branched-chain keto acid dehydrogenase complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, encoded by PPARGC1A), 61% of the analysed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific Ppargc1a knockout mice. ESRRA (encoding ERRα) silencing completely abrogated the PGC-1α-induced upregulation of BCAA-related genes in primary human myotubes. Conclusions/interpretation Metabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease in circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via PGC-1α is ERRα-dependent. Graphical abstract

The impact of leucine infusion on skeletal muscle amino acid and energy metabolism in severely traumatized patients

1992 ◽  
Vol 11 (3) ◽  
pp. 140-146 ◽  
Author(s):  
C. Lennmarken ◽  
S. Skullman ◽  
M. Wirén ◽  
E. Vinnars ◽  
J. Larsson
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Energy Metabolism ◽  
The Impact

scholarly journals Markers of Metabolism in Skeletal Muscle and White Adipose Tissue are Distinctly Altered by Differing Dietary Oils in ob/ob Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 661-661
Author(s):  
Deena Snoke ◽  
Rachel Cole ◽  
Genevieve Sparagna ◽  
Martha Belury
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Grip Strength ◽  
White Adipose Tissue ◽  
Lipid Storage ◽  
Cross Sectional ◽  
Dietary Oils ◽  
Funding Sources ◽  
The Impact ◽  
Development Center

Abstract Objectives Investigate the impact of LA-rich oil (LO) on measures of energy metabolism in a mouse model of metabolic syndrome. Methods Ob/ob mice were fed diets containing 6% wt LO, oleic acid-rich (OO) or palmitic acid-rich (PO) for 6 weeks. Body composition was measured at weeks 0 and 6. Plasma was collected at necropsy to measure adiponectin, insulin, and glucose. Grip strength and muscle fiber cross-sectional area (CSA) of total and succinate dehydrogenase-positive (SDH) fibers were quantified in quadriceps. In white adipose tissue, mRNA was measured for markers of beiging and lipid storage. Results Mice fed OO and LO diets (vs. PO diet) had reduced % adipose. There was no difference of oils on plasma adiponectin or HOMA-IR. Decreases in grip strength were observed in PO-fed mice, while OO and LO-fed mice maintained strength throughout the study. LO-fed mice exhibited smaller skeletal muscle fibers compared to the PO-fed mice. OO-fed mice had fewer intermediate-sized SDH fibers. In white adipose tissue, LO-fed mice exhibited increased PGC1a, and decreased PPARy and LPL mRNA compared to PO-fed mice. Conclusions These findings suggest that dietary LA may alter lipid mobilization and metabolism in obese mice. These preliminary results showcase the importance of future investigation of lipid storage and mitochondrial phospholipid biology in skeletal muscle. Funding Sources Funding was provided by NIH R21CA185140, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship. DBS received support from the AOCS Thomas H. Smouse Memorial Fellowship.

scholarly journals The impact of severe burns on skeletal muscle mitochondrial function

Burns ◽  
2013 ◽  
Vol 39 (6) ◽  
pp. 1039-1047 ◽  
Author(s):  
Craig Porter ◽  
David N. Herndon ◽  
Labros S. Sidossis ◽  
Elisabet Børsheim
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Severe Burns ◽  
The Impact

scholarly journals Lipid droplets contribute myogenic differentiation in C2C12 by promoting the remodeling of the acstin-filament

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Yanjie Tan ◽  
Yi Jin ◽  
Pengxiang Zhao ◽  
Jian Wu ◽  
Zhuqing Ren
Keyword(s):  
Skeletal Muscle ◽  
Actin Filaments ◽  
Lipid Droplets ◽  
Myogenic Differentiation ◽  
C2c12 Myoblast ◽  
Cellular Processes ◽  
Myoblast Cells ◽  
Athlete’S Paradox ◽  
The Impact ◽  
Insight Into

AbstractLipid droplet (LD), a multi-functional organelle, is found in most eukaryotic cells. LDs participate in the regulation of many cellular processes including proliferation, stress, and apoptosis. Previous studies showed the athlete’s paradox that trained athletes accumulate LDs in their skeletal muscle. However, the impact of LDs on skeletal muscle and myogenesis is not clear. We discovered that C2C12 myoblast cells containing more LDs formed more multinucleated muscle fibers. We also discovered that LDs promoted cell migration and fusion by promoting actin-filaments remodeling. Mechanistically, two LD-proteins, Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), medicated the recruitment of actinin proteins which contributed to actin-filaments formation on the surface of LDs. During remodeling, the actinin proteins on LDs surface translocated to actin-filaments via ARF1/COPI vesicles. Our study demonstrate LDs contribute to cell differentiation, which lead to new insight into the LD function.

scholarly journals The historical context and scientific legacy of John O. Holloszy

2019 ◽  
Vol 127 (2) ◽  
pp. 277-305 ◽  
Author(s):  
James M. Hagberg ◽  
Edward F. Coyle ◽  
Kenneth M. Baldwin ◽  
Gregory D. Cartee ◽  
Luigi Fontana ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Caloric Restriction ◽  
Exercise Physiology ◽  
Historical Context ◽  
Cross Sectional ◽  
Insulin Metabolism ◽  
Scientific Legacy ◽  
Muscle Plasticity ◽  
The Impact

John O. Holloszy, as perhaps the world’s preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy’s outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.

scholarly journals The Impact of Skeletal Muscle ERα on Mitochondrial Function and Metabolic Health

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Andrea L Hevener ◽  
Vicent Ribas ◽  
Timothy M Moore ◽  
Zhenqi Zhou
Keyword(s):  
Skeletal Muscle ◽  
Chronic Disease ◽  
Mitochondrial Function ◽  
Disease Risk ◽  
Hormone Replacement ◽  
Treatment Strategies ◽  
Metabolic Health ◽  
Metabolic Dysfunction ◽  
The Metabolic Syndrome ◽  
The Impact

Abstract The incidence of chronic disease is elevated in women after menopause. Increased expression of ESR1 (the gene that encodes the estrogen receptor alpha, ERα) in muscle is highly associated with metabolic health and insulin sensitivity. Moreover, reduced muscle expression levels of ESR1 are observed in women, men, and animals presenting clinical features of the metabolic syndrome (MetSyn). Considering that metabolic dysfunction elevates chronic disease risk, including type 2 diabetes, heart disease, and certain cancers, treatment strategies to combat metabolic dysfunction and associated pathologies are desperately needed. This review will provide published work supporting a critical and protective role for skeletal muscle ERα in the regulation of mitochondrial function, metabolic homeostasis, and insulin action. We will provide evidence that muscle-selective targeting of ERα may be effective for the preservation of mitochondrial and metabolic health. Collectively published findings support a compelling role for ERα in the control of muscle metabolism via its regulation of mitochondrial function and quality control. Studies identifying ERα-regulated pathways essential for disease prevention will lay the important foundation for the design of novel therapeutics to improve metabolic health of women while limiting secondary complications that have historically plagued traditional hormone replacement interventions.

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