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 The effect of toll-like receptor ligands on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ragna H. Tingstad ◽  
Frode Norheim ◽  
Fred Haugen ◽  
Yuan Z. Feng ◽  
Hege S. Tunsjø ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oleic Acid ◽  
Energy Metabolism ◽  
Glucose Metabolism ◽  
Human Skeletal Muscle ◽  
Acid Metabolism ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Metabolic Effects ◽  
Human Skeletal Muscle Cells

AbstractSkeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus. The aim of the present study was to determine if ligands of Toll-like receptors (TLRs) could have an impact on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells. The myotubes expressed mRNA for TLRs 1–6. TLR3, TLR4, TLR5 and TLR6 ligands (TLRLs) increased glucose metabolism. Furthermore, TLR4L and TLR5L increased oleic acid metabolism. The metabolic effects of TLRLs were not evident until after at least 24 h pre-incubation of the cells and here the metabolic effects were more evident for the metabolism of glucose than oleic acid, with a shift towards effects on oleic acid metabolism after chronic exposure (168 h). However, the stimulatory effect of TLRLs on myokine expression and secretion was detected after only 6 h, where TLR3-6L stimulated secretion of interleukin-6 (IL-6). TLR5L also increased secretion of interleukin-8 (IL-8), while TLR6L also increased secretion of granulocyte–macrophage colony stimulating factor (GM-CSF). Pre-incubation of the myotubes with IL-6 for 24 h increased oleic acid oxidation but had no effect on glucose metabolism. Thus IL-6 did not mimic all the metabolic effects of the TLRLs, implying metabolic effects beyond the actions of this myokine.

scholarly journals γ-Linolenic acid increases expression of key regulators of lipid metabolism in human skeletal muscle cells

2019 ◽  
Author(s):  
L.A Baker ◽  
N.R.W Martin ◽  
D.J Player ◽  
M.P Lewis
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Linolenic Acid ◽  
Metabolic Diseases ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Of Genes ◽  
Human Myotubes ◽  
Human Skeletal Muscle Cells

AbstractControl of skeletal muscle fat metabolism is regulated acutely through Peroxisome Proliferator Activated Receptor (PPAR) δ activation and its downstream intracellular targets. The purpose of this study was to determine whether fatty acids with high binding affinity for PPARδ can elevate the expression of genes related to fatty acid oxidation and indicators of mitochondrial biogenesis in cultured human skeletal myotubes. Myotubes were treated for 72 hours with one of four conditions: (i) Control (CON); (ii) Eicosapentaenoic acid (EPA 250μM); (iii) γ-linolenic acid (γ-LA 250μM); (iv) PPARδ Agonist (GW501516 10nM). Incubation with γ-LA induced increases in the gene expression of CD36 (p= 0.005), HADHA (p= 0.022) and PDK4 (p=0.025) in comparison with CON, with no further differences observed between conditions. Furthermore, intensity of MitoTracker® Red immunostaining in myotubes increased following incubation with γ-LA (p≤ 0.001) and EPA (p= 0.005) however these trends were not mirrored in the expression of PGC-1α as might be expected. Overall, γ-LA elevates levels the transcription of key intracellular regulators of lipid metabolism and transport in human myotubes, which may be clinically beneficial in the control of metabolic diseases.

scholarly journals Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes

2019 ◽  
Vol 16 (7) ◽  
pp. 1157 ◽  
Author(s):  
Hyo-Bum Kwak ◽  
Tracey Woodlief ◽  
Thomas Green ◽  
Julie Cox ◽  
Robert Hickner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Radical ◽  
Fatty Acid Oxidation ◽  
Insulin Signaling ◽  
Human Skeletal Muscle ◽  
Acid Oxidation ◽  
Protein Levels ◽  
Human Skeletal Muscle Cells ◽  
Mitochondrial Fatty Acid

In rodent skeletal muscle, acyl-coenzyme A (CoA) synthetase 5 (ACSL-5) is suggested to localize to the mitochondria but its precise function in human skeletal muscle is unknown. The purpose of these studies was to define the role of ACSL-5 in mitochondrial fatty acid metabolism and the potential effects on insulin action in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (obese women (body mass index (BMI) = 34.7 ± 3.1 kg/m2)) were transfected with ACSL-5 plasmid DNA or green fluorescent protein (GFP) vector (control), differentiated into myotubes, and harvested (7 days). HSKMC were assayed for complete and incomplete fatty acid oxidation ([1-14C] palmitate) or permeabilized to determine mitochondrial respiratory capacity (basal (non-ADP stimulated state 4), maximal uncoupled (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP)-linked) respiration, and free radical (superoxide) emitting potential). Protein levels of ACSL-5 were 2-fold higher in ACSL-5 overexpressed HSKMC. Both complete and incomplete fatty acid oxidation increased by 2-fold (p < 0.05). In permeabilized HSKMC, ACSL-5 overexpression significantly increased basal and maximal uncoupled respiration (p < 0.05). Unexpectedly, however, elevated ACSL-5 expression increased mitochondrial superoxide production (+30%), which was associated with a significant reduction (p < 0.05) in insulin-stimulated p-Akt and p-AS160 protein levels. We concluded that ACSL-5 in human skeletal muscle functions to increase mitochondrial fatty acid oxidation, but contrary to conventional wisdom, is associated with increased free radical production and reduced insulin signaling.

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.

3,5-Diiodo-l-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement

2009 ◽  
Vol 296 (3) ◽  
pp. E497-E502 ◽  
Author(s):  
A. Lombardi ◽  
P. de Lange ◽  
E. Silvestri ◽  
R. A. Busiello ◽  
A. Lanni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Atp Synthesis ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Amp Activated Protein Kinase

Triiodothyronine regulates energy metabolism and thermogenesis. Among triiodothyronine derivatives, 3,5-diiodo-l-thyronine (T2) has been shown to exert marked effects on energy metabolism by acting mainly at the mitochondrial level. Here we investigated the capacity of T2 to affect both skeletal muscle mitochondrial substrate oxidation and thermogenesis within 1 h after its injection into hypothyroid rats. Administration of T2 induced an increase in mitochondrial oxidation when palmitoyl-CoA (+104%), palmitoylcarnitine (+80%), or succinate (+30%) was used as substrate, but it had no effect when pyruvate was used. T2 was able to 1) activate the AMPK-ACC-malonyl-CoA metabolic signaling pathway known to direct lipid partitioning toward oxidation and 2) increase the importing of fatty acids into the mitochondrion. These results suggest that T2 stimulates mitochondrial fatty acid oxidation by activating several metabolic pathways, such as the fatty acid import/β-oxidation cycle/FADH2-linked respiratory pathways, where fatty acids are imported. T2 also enhanced skeletal muscle mitochondrial thermogenesis by activating pathways involved in the dissipation of the proton-motive force not associated with ATP synthesis (“proton leak”), the effect being dependent on the presence of free fatty acids inside mitochondria. We conclude that skeletal muscle is a target for T2, and we propose that, by activating processes able to enhance mitochondrial fatty acid oxidation and thermogenesis, T2 could play a role in protecting skeletal muscle against excessive intramyocellular lipid storage, possibly allowing it to avoid functional disorders.

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells

2015 ◽  
Vol 217 (1) ◽  
pp. 45-60 ◽  
Author(s):  
M. Hjorth ◽  
S. Pourteymour ◽  
S. W. Görgens ◽  
T. M. Langleite ◽  
S. Lee ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

scholarly journals Mechanisms of Energy Metabolism in Skeletal Muscle Mitochondria Following Radiation Exposure

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 950 ◽  
Author(s):  
Kim ◽  
Lee ◽  
Kim ◽  
Kim ◽  
Yi
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Ionizing Radiation ◽  
Radiation Exposure ◽  
Biological Effects ◽  
Mitochondrial Protein ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Mitochondrial Energy Metabolism ◽  
Effects Of Radiation

An understanding of cellular processes that determine the response to ionizing radiation exposure is essential for improving radiotherapy and assessing risks to human health after accidental radiation exposure. Radiation exposure leads to many biological effects, but the mechanisms underlying the metabolic effects of radiation are not well known. Here, we investigated the effects of radiation exposure on the metabolic rate and mitochondrial bioenergetics in skeletal muscle. We show that ionizing radiation increased mitochondrial protein and mass and enhanced proton leak and mitochondrial maximal respiratory capacity, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, mice and cells treated with radiation became energetically efficient and displayed increased fatty acid and amino acid oxidation metabolism through the citric acid cycle. Finally, we demonstrate that radiation-induced alterations in mitochondrial energy metabolism involved adenosine monophosphate-activated kinase signaling in skeletal muscle. Together, these results demonstrate that alterations in mitochondrial mass and function are important adaptive responses of skeletal muscle to radiation.

scholarly journals Effects of Arginine and Inflammation on Protein Metabolism in Human Skeletal Muscle Cells (P01-034-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lauren Varvatos ◽  
Jamie Blum ◽  
Janet Back ◽  
Anna Thalacker-Mercer
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Cells ◽  
Radioactive Isotopes ◽  
Treatment Control ◽  
Additional Increase ◽  
Arginine Uptake ◽  
Age Related ◽  
Human Myotubes ◽  
Human Skeletal Muscle Cells

Abstract Objectives Chronic inflammation is a hallmark of skeletal muscle (SkM) with advancing age and is thought to augment age-related SkM atrophy (sarcopenia). Arginine, a conditionally essential amino acid, is necessary for protein synthesis. Intriguingly, arginine has been identified as being important for attenuating nuclear factor kappa B (NF-κB) activity in non-muscle cells. Our objective was to determine the age-related effects of arginine and inflammation on markers of protein synthesis and breakdown in human myotubes. Methods Muscle progenitor cells (MPCs) were obtained from SkM biopsy tissue of young (YNG, n = 5) and old (OLD, n = 5) women. MPCs were differentiated for 5 days (myotubes) followed by treatment with a pro-inflammatory cytokine, TNFα, for 6 h, 24 h, 48 h, or 96 h. Inflammatory activity and arginine uptake were determined using immunoblotting and radioactive isotopes. Protein synthesis was assessed with puromycin incorporation. MURF1 and MAFBX1 gene expression were used as indicators of proteolysis. Results Prior to TNFα treatment, OLD (vs. YNG) myotubes had greater arginine uptake (P = 0.02), but there were no age-related differences in basal p65 NF-κB activity, puromycin incorporation, or MAFBX1 and MURF1 expression (P > 0.05). Treatment with TNFα induced NF-κB activity in both YNG and OLD myotubes at 6 and 24 h of treatment (P < 0.0001), with no additional increase in activity from 24–96 h. CAT2, an arginine transporter, was transiently induced at 6 h of TNFα treatment (P < 0.01), with no age-related difference in response (P > 0.05). 96 h of TNFα increased arginine uptake in OLD (P < 0.05), but not YNG myotubes (P > 0.05). 6 h TNFα had no effect (P > 0.05), but 96 h of TNFα reduced puromycin incorporation in both YNG and OLD myotubes (P < 0.05). Compared to no treatment control, 96 h TNFα unexpectedly decreased MAFBX1 expression in both YNG and OLD myotubes (P < 0.001). Intriguingly, in the presence of TNFα, arginine increased MURF1 expression in YNG and OLD myotubes compared to no treatment control (P < 0.05). Conclusions Unexpectedly, arginine amplified markers of proteolysis, and did not affect protein synthesis. Future studies will investigate regulatory transcription factors involved in protein breakdown and a crude marker of protein balance (e.g., myotube diameter). Funding Sources President's Council for Cornell Women.

scholarly journals Is There a Metabolic Program in the Skeletal Muscle of Obese Individuals?

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Joseph A. Houmard ◽  
Walter J. Pories ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Bypass Surgery ◽  
Severe Obesity ◽  
Gastric Bypass Surgery ◽  
Acid Oxidation ◽  
Genetic Origin ◽  
Human Skeletal Muscle Cells ◽  
Severely Obese

Severe obesity (BMI ≥ 40 kg/m2) is associated with multiple defects in skeletal muscle which contribute to insulin resistance and a reduction in fatty acid oxidation (FAO) in this tissue. These metabolic derangements are retained in human skeletal muscle cells raised in culture. Together, these findings are indicative of a dysfunctional global metabolic program with severe obesity which is of an epigenetic or genetic origin. Weight loss via gastric bypass surgery can “turn off” and/or correct components of this metabolic program as insulin sensitivity is restored; however, the impairment in FAO in skeletal muscle remains evident. Physical activity can improve FAO and insulin action, indicating that this patient population is not exercise resistant and that exercise offers a pathway to circumvent the abnormal program. Findings presented in this review will hopefully increase the understanding of and aid in preventing and/or treating the severely obese condition.

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