scholarly journals High Insulin Combined With Essential Amino Acids Stimulates Skeletal Muscle Mitochondrial Protein Synthesis While Decreasing Insulin Sensitivity in Healthy Humans

2014 ◽  
Vol 99 (12) ◽  
pp. E2574-E2583 ◽  
Author(s):  
Matthew M. Robinson ◽  
Mattias Soop ◽  
Tae Seo Sohn ◽  
Dawn M. Morse ◽  
Jill M. Schimke ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Insulin Sensitivity ◽  
Mitochondrial Protein ◽  
Essential Amino Acids ◽  
Mitochondrial Protein Synthesis ◽  
Healthy Humans ◽  
High Insulin

scholarly journals Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment

2017 ◽  
Vol 313 (5) ◽  
pp. E552-E562 ◽  
Author(s):  
Sean A. Newsom ◽  
Benjamin F. Miller ◽  
Karyn L. Hamilton ◽  
Sarah E. Ehrlicher ◽  
Harrison D. Stierwalt ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Insulin Sensitivity ◽  
Mitochondrial Respiration ◽  
High Fat Diet ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
High Fat ◽  
The Impact

Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10–12. High-resolution respirometry was performed using palmitoyl-l-carnitine, glutamate+malate, and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation were increased in mice consuming a high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H2O2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with a high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance.

scholarly journals Skeletal muscle mitochondrial protein synthesis and respiration in response to the energetic stress of an ultra-endurance race

2017 ◽  
Vol 123 (6) ◽  
pp. 1516-1524 ◽  
Author(s):  
Adam R. Konopka ◽  
William M. Castor ◽  
Christopher A. Wolff ◽  
Robert V. Musci ◽  
Justin J. Reid ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Endurance Exercise ◽  
Mitochondrial Respiration ◽  
Endurance Athlete ◽  
Control Period ◽  
Mitochondrial Protein ◽  
Mitochondrial Bioenergetics ◽  
Mitochondrial Protein Synthesis ◽  
Ultra Endurance

The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m to complete 800 km and 21,000 m of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR. Titrated and bolus doses of ADP were provided to determine substrate-specific oxidative phosphorylation (OXPHOS) and electron transport system (ETS) capacities in permeabilized muscle fibers via high-resolution respirometry. Protein synthetic rates were determined by daily oral consumption of deuterium oxide (2H2O). The endurance athlete had OXPHOS (226 pmol·s−1·mg tissue−1) and ETS (231 pmol·s−1·mg tissue−1) capacities that rank among the highest published to date in humans. Mitochondrial (3.2-fold), cytoplasmic (2.3-fold), and myofibrillar (1.5-fold) protein synthesis rates were greater during CTR compared with CON. With titrated ADP doses, the apparent Km of ADP, OXPHOS, and ETS increased after the CTR. With provision of ADP boluses after the CTR, the addition of fatty acids (−12 and −14%) mitigated the decline in OXPHOS and ETS capacity during carbohydrate-supported respiration (−26 and −31%). In the face of extreme stresses during the CTR, elevated rates of mitochondrial protein synthesis may contribute to rapid adaptations in mitochondrial bioenergetics. NEW & NOTEWORTHY The mechanisms that maintain skeletal muscle function during extreme stresses remain incompletely understood. In the current study, greater rates of mitochondrial protein synthesis during the energetic demands of ultra-endurance exercise may contribute to rapid adaptations in mitochondrial bioenergetics. The endurance athlete herein achieved mitochondrial respiratory capacities among the highest published for humans. Greater mitochondrial protein synthesis during ultra-endurance exercise may contribute to improved mitochondrial respiration and serve as a mechanism to resist cellular energetic stresses.

scholarly journals Chronic rapamycin administration maintains mitochondrial protein synthesis in heart and skeletal muscle

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Joshua Drake ◽  
Frederick F. Peelor ◽  
Laurie M. Biela ◽  
Richard A. Miller ◽  
Karyn L. Hamilton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis

Properties of skeletal muscle mitochondria isolated from subsarcolemmal and intermyofibrillar regions

1993 ◽  
Vol 264 (2) ◽  
pp. C383-C389 ◽  
Author(s):  
A. M. Cogswell ◽  
R. J. Stevens ◽  
D. A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Mitochondrial Protein ◽  
Mitochondrial Fraction ◽  
Biochemical Properties ◽  
Leucine Incorporation ◽  
Mitochondrial Protein Synthesis ◽  
Skeletal Muscle Mitochondria ◽  
Mitochondrial Fractions

Two mitochondrial fractions, termed intermyofibrillar (IMF) and subsarcolemmal (SS), were isolated from skeletal muscle, and their biochemical properties were related to differences in respiration and mitochondrial protein synthesis. State III respiration was 2.3- to 2.8-fold greater in IMF than in SS mitochondria. Site 1 inhibition of respiration with rotenone reduced this difference to 1.4-fold. When sites 1 and 2 were inhibited with antimycin, the 1.4-fold differences remained. The activities of cytochrome-c oxidase (CYTOX) and succinate dehydrogenase (SDH) could account for some of these differences, since CYTOX was 20% greater (P < 0.05) in IMF mitochondria, and SDH was 40% greater (P < 0.05) in SS mitochondria. Cytochromes a, b, c, and c1 contents were similar in the two fractions. Cardiolipin (CL) content was higher (P < 0.05) in SS mitochondria, indicating a less dense mitochondrial fraction with respect to CL. In vitro [3H]leucine incorporation was 1.8-fold higher (P < 0.05) in IMF than in SS mitochondria. Thus compositional differences between IMF and SS fractions exist, perhaps representing mitochondria at different stages of biogenesis. The biochemical and functional differences could not solely be due to differences in mitochondrial protein synthesis but could also be due to nuclear-directed protein synthesis specific to each mitochondrial fraction.

Optimizing the measurement of mitochondrial protein synthesis in human skeletal muscle

2015 ◽  
Vol 40 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Nicholas A. Burd ◽  
Nicolas Tardif ◽  
Olav Rooyackers ◽  
Luc J.C. van Loon
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Human Skeletal Muscle ◽  
Contractile Activity ◽  
Mitochondrial Protein ◽  
Exercise Bout ◽  
Performance Outcomes ◽  
Mitochondrial Protein Synthesis ◽  
Practical Guidelines ◽  
And Performance

The measurement of mitochondrial protein synthesis after food ingestion, contractile activity, and/or disease is often used to provide insight into skeletal muscle adaptations that occur in the longer term. Studies have shown that protein ingestion stimulates mitochondrial protein synthesis in human skeletal muscle. Minor differences in the stimulation of mitochondrial protein synthesis occur after a single bout of resistance or endurance exercise. There appear to be no measurable differences in mitochondrial protein synthesis between critically ill patients and aged-matched controls. However, the mitochondrial protein synthetic response is reduced at a more advanced age. In this paper, we discuss the challenges involved in the measurement of human skeletal muscle mitochondrial protein synthesis rates based on stable isotope amino acid tracer methods. Practical guidelines are discussed to improve the reliability of the measurement of mitochondrial protein synthesis rates. The value of the measurement of mitochondrial protein synthesis after a single meal or exercise bout on the prediction of the longer term skeletal muscle mass and performance outcomes in both the healthy and disease populations requires more work, but we emphasize that the measurements need to be reliable to be of any value to the field.

scholarly journals Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats

2020 ◽  
Vol 30 (2) ◽  
pp. 153-164 ◽  
Author(s):  
Andrew M. Holwerda ◽  
Freek G. Bouwman ◽  
Miranda Nabben ◽  
Ping Wang ◽  
Janneau van Kranenburg ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Atp Synthase ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mitochondrial Protein ◽  
Experimental Period ◽  
Mitochondrial Protein Synthesis ◽  
The Impact

Physical activity increases muscle protein synthesis rates. However, the impact of exercise on the coordinated up- and/or downregulation of individual protein synthesis rates in skeletal muscle tissue remains unclear. The authors assessed the impact of exercise on mixed muscle, myofibrillar, and mitochondrial protein synthesis rates as well as individual protein synthesis rates in vivo in rats. Adult Lewis rats either remained sedentary (n = 3) or had access to a running wheel (n = 3) for the last 2 weeks of a 3-week experimental period. Deuterated water was injected and subsequently administered in drinking water over the experimental period. Blood and soleus muscle were collected and used to assess bulk mixed muscle, myofibrillar, and mitochondrial protein synthesis rates using gas chromatography–mass spectrometry and individual muscle protein synthesis rates using liquid chromatography–mass spectrometry (i.e., dynamic proteomic profiling). Wheel running resulted in greater myofibrillar (3.94 ± 0.26 vs. 3.03 ± 0.15%/day; p < .01) and mitochondrial (4.64 ± 0.24 vs. 3.97 ± 0.26%/day; p < .05), but not mixed muscle (2.64 ± 0.96 vs. 2.38 ± 0.62%/day; p = .71) protein synthesis rates, when compared with the sedentary condition. Exercise impacted the synthesis rates of 80 proteins, with the difference from the sedentary condition ranging between −64% and +420%. Significantly greater synthesis rates were detected for F1-ATP synthase, ATP synthase subunit alpha, hemoglobin, myosin light chain-6, and synaptopodin-2 (p < .05). The skeletal muscle protein adaptive response to endurance-type exercise involves upregulation of mitochondrial protein synthesis rates, but it is highly coordinated as reflected by the up- and downregulation of various individual proteins across different bulk subcellular protein fractions.

scholarly journals The impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men: clinical efficacy of pulse vs. bolus supply

2015 ◽  
Vol 309 (5) ◽  
pp. E450-E457 ◽  
Author(s):  
W. Kyle Mitchell ◽  
Bethan E. Phillips ◽  
John P. Williams ◽  
Debbie Rankin ◽  
Jonathan N. Lund ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Blood Flow ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Older Men ◽  
Essential Amino Acids ◽  
Low Amplitude ◽  
The Impact

Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of “slow” or “fast” protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (∼70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 × 3.75 g every 45 min; n = 8) during 13C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 μiU/ml 25-min postfeed), essential aminoacidemia (∼3,000 μM, 45–65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (∼1,800 μM 80–195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the “muscle-full” effect permitted identical MPS following low-amplitude-sustained EAA exposure.

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