Mechanisms of ageing metabolic decline revealed by targeted metabolomics and energy metabolism in NAD+ depleted skeletal muscle

2016 ◽  
Author(s):  
Rachel Fletcher ◽  
Lucy Oldacre-Bartley ◽  
Craig Doig ◽  
Charles Brenner ◽  
Gareth Lavery
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Targeted Metabolomics

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

scholarly journals The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

2011 ◽  
Vol 53 (3) ◽  
pp. 577-586 ◽  
Author(s):  
Jeffrey D. Browning ◽  
Jeannie Baxter ◽  
Santhosh Satapati ◽  
Shawn C. Burgess
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Short Term ◽  
Muscle Lipid ◽  
Healthy Women ◽  
Skeletal Muscle Lipid

scholarly journals Exercise-Induced Alterations in Skeletal Muscle, Heart, Liver, and Serum Metabolome Identified by Non-Targeted Metabolomics Analysis

Metabolites ◽  
2017 ◽  
Vol 7 (3) ◽  
pp. 40 ◽  
Author(s):  
Joseph Starnes ◽  
Traci Parry ◽  
Sara O’Neal ◽  
James Bain ◽  
Michael Muehlbauer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Targeted Metabolomics ◽  
Exercise Induced ◽  
Metabolomics Analysis

scholarly journals Substrate oxidation in primary human skeletal muscle cells is influenced by donor age

2020 ◽  
Vol 382 (3) ◽  
pp. 599-608
Author(s):  
Vigdis Aas ◽  
G. Hege Thoresen ◽  
Arild C. Rustan ◽  
Jenny Lund
Keyword(s):  
Skeletal Muscle ◽  
Oleic Acid ◽  
Energy Metabolism ◽  
Substrate Oxidation ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Donor Age ◽  
Human Myotubes ◽  
Human Skeletal Muscle Cells

AbstractPrimary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e., musculus vastus lateralis, musculus obliquus internus abdominis, and musculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.

scholarly journals Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

JCI Insight ◽  
2018 ◽  
Vol 3 (9) ◽  
Author(s):  
Steve Lancel ◽  
Matthijs K.C. Hesselink ◽  
Estelle Woldt ◽  
Yves Rouillé ◽  
Emilie Dorchies ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Endurance Capacity ◽  
Muscle Energy ◽  
Muscle Energy Metabolism

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

Effects of the Anti-Migraine Drug Sumatriptan on Muscle Energy Metabolism: Relationship to Side-Effects

Cephalalgia ◽  
2000 ◽  
Vol 20 (1) ◽  
pp. 39-44 ◽  
Author(s):  
MD Boska ◽  
KMA Welch ◽  
L Schultz ◽  
J Nelson
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Side Effects ◽  
Kinetic Data ◽  
Oxygen Storage ◽  
Resonance Spectroscopy ◽  
Sumatriptan Succinate ◽  
Muscle Energy ◽  
Creatine Kinase Reaction ◽  
Muscle Energy Metabolism

Sumatriptan succinate (Imitrex) is a 5-HT(5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5–20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.

Abstract 13921: Targeting Receptor-Interacting Protein 140 to Modulate Energy Metabolism in the Failing Heart

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tsunehisa Yamamoto ◽  
Elizabeth Pruzinsky ◽  
Kirill Batmanov ◽  
Daniel P Kelly
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Interacting Protein ◽  
Failing Heart ◽  
Metabolic Genes ◽  
Cardiac Energy

The nuclear receptors, peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and their co-regulator PPARγ coactivator-1α (PGC-1α), control postnatal cardiac mitochondrial biogenesis and energy metabolism. During the development of heart failure (HF), the activity of PGC-1/PPAR/ERR is reduced resulting in diminished capacity for fatty acid oxidation (FAO) and ATP production potentially contributing to an “energy-starved” state that contributes to progression of HF. Receptor-Interacting protein 140 (RIP140) serves as a co-repressor of PGC-1/PPAR/ERR in skeletal muscle and adipose tissue. We hypothesized that RIP140 represses cardiac energy metabolism in the normal and failing heart. Accordingly, we targeted Nrip1 (encoding RIP140) using a muscle creatinine kinase (MCK)-driven Cre recombinase to generate striated muscle-specific RIP140 knockout (msRIP140 KO) mice. msRIP140 KO mice appeared normal at baseline with no difference in survival or cardiac systolic function compared to littermate controls. RNA-sequence analysis demonstrated that the expression of genes involved in a wide array of mitochondrial energy metabolic pathways including FAO, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and branched-chain amino acid (BCAA) degradation pathways were upregulated in msRIP140 KO ventricles, and in msRIP140 KO skeletal muscle. msRIP140 KO mice exhibited significantly less cardiac hypertrophy and diastolic dysfunction in response to chronic pressure overload. Next, cardiac-specific (cs) RIP140 KO mice were generated and subjected to transverse aortic constriction/apical myocardial infarction surgery (TAC/MI), an established HF model. csRIP140 KO mice exhibited less cardiac remodeling and systolic dysfunction compared to littermate controls, along with less downregulation of metabolic genes and induction of cardiac stress ( Nppa and Nppb ) and fibrosis response markers ( Tgfb2 and Col3a1 ). We conclude that RIP140 serves as a global co-repressor of cardiac energy metabolic genes in the adult heart and that modulation of RIP140 activity could prove to be a novel therapeutic approach for HF.

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