scholarly journals Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling

2013 ◽  
Vol 304 (3) ◽  
pp. E282-E293 ◽  
Author(s):  
Charles Harris ◽  
Donald J. Roohk ◽  
Mark Fitch ◽  
Benjamin M. Boudignon ◽  
Bernard P. Halloran ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Collagen Synthesis ◽  
Muscle Protein ◽  
Subcutaneous Fat ◽  
Skin Thickness ◽  
Breakdown Rate ◽  
Triglyceride Synthesis ◽  
Fat Depots ◽  
Breakdown Rates ◽  
Skin Collagen

Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)+ mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg+ mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg+ mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg+ mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg+ mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg+ mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue.

scholarly journals Skeletal-muscle growth and protein turnover

1975 ◽  
Vol 150 (2) ◽  
pp. 235-243 ◽  
Author(s):  
D J Millward ◽  
P J Garlick ◽  
R J C Stewart ◽  
D O Nnanyelugo ◽  
J C Waterlow
Keyword(s):  
Skeletal Muscle ◽  
Growth Rate ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Muscle Size ◽  
Synthesis Rate ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Breakdown Rates

Because of turnover, protein synthesis and breakdown can each be involved in the regulation of the growth of tissue protein. To investigate the regulation of skeletal-muscle-protein growth we measured rates of protein synthesis and breakdown in growing rats during development on a good diet, during development on a marginally low-protein diet and during rehabilitation on a good diet after a period of severe protein deficiency. Rates of protein synthesis were measured in vivo with a constant intravenous infusion of [14C]tyrosine. The growth rate of muscle protein was measured and the rate of breakdown calculated as breakdown rate=synthesis rate-growth rate. These measurements showed that during development on a good diet there was a fall with age in the rate of protein synthesis resulting from a fall in capacity (RNA concentration) and activity (synthesis rate per unit of RNA). There was a fall with age in the breakdown rate so that the rate was highest in the weaning rats, with a half-life of 3 days. There was a direct correlation between the fractional growth and breakdown rates. During rehabilitation on the good diet, rapid growth was also accompanied by high rates of protein breakdown. During growth on the inadequate diet protein synthesis rates were lesss than in controls, but growth occurred because of decreased rates of protein breakdown. This compression was not complete, however, since ultimate muscle size was only one-half that of controls. It is suggested that increased rates of protein breakdown are a necessary accompaniment to muscle growth and may result from the way in which myofibrils proliferate.

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

2005 ◽  
Vol 288 (4) ◽  
pp. E645-E653 ◽  
Author(s):  
René Koopman ◽  
Anton J. M. Wagenmakers ◽  
Ralph J. F. Manders ◽  
Antoine H. G. Zorenc ◽  
Joan M. G. Senden ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Vastus Lateralis Muscle ◽  
Protein Balance ◽  
Body Protein ◽  
Breakdown Rates ◽  
Postexercise Recovery ◽  
Male Subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of l-[ ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 ± 19% and +77 ± 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial ( P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials ( P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 ± 0.006 vs. 0.061 ± 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 ± 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.

scholarly journals Treatment of burned rats with insulin-like growth factor I inhibits the catabolic response in skeletal muscle

1998 ◽  
Vol 275 (4) ◽  
pp. R1091-R1098 ◽  
Author(s):  
Cheng-Hui Fang ◽  
Bing-Guo Li ◽  
Jing Jing Wang ◽  
Josef E. Fischer ◽  
Per-Olof Hasselgren
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Burn Injury ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Breakdown ◽  
Turnover Rates ◽  
Breakdown Rates ◽  
Igf I ◽  
Catabolic Response

Thermal injury is associated with a pronounced catabolic response in skeletal muscle, reflecting inhibited protein synthesis and increased protein breakdown, in particular myofibrillar protein breakdown. Administration of insulin-like growth factor I (IGF-I) has a nitrogen-sparing effect after burn injury, but the influence of this treatment on protein turnover rates in skeletal muscle is not known. In the present study, we examined the effect of IGF-I on muscle protein synthesis and breakdown rates following burn injury in rats. After a 30% total body surface area burn injury or sham procedure, rats were treated with a continuous infusion of IGF-I (3.5 or 7 mg ⋅ kg−1 ⋅ 24 h−1) for 24 h. Protein synthesis and breakdown rates were determined in incubated extensor digitorum longus muscles. Burn injury resulted in increased total and myofibrillar protein breakdown rates and reduced protein synthesis in muscle. The increase in protein breakdown rates was blocked by both doses of IGF-I and the burn-induced inhibition of muscle protein synthesis was partially reversed by the higher dose of the hormone. IGF-I did not influence muscle protein turnover rates in nonburned rats. The results suggest that the catabolic response to burn injury in skeletal muscle can be inhibited by IGF-I.

scholarly journals Dileucine ingestion is more effective than leucine in stimulating muscle protein turnover in young males: a double blind randomized controlled trial

2021 ◽  
Author(s):  
Kevin J. M. Paulussen ◽  
Rafael A. Alamilla ◽  
Amadeo F. Salvador ◽  
Colleen F. McKenna ◽  
Andrew T. Askow ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Controlled Trial ◽  
Young Men ◽  
Double Blind ◽  
Muscle Protein Turnover ◽  
Breakdown Rates ◽  
Over Time

Leucine is regarded as an anabolic trigger for the mTORC1 pathway and the stimulation muscle protein synthesis rates. More recently, there has been an interest in underpinning the relevance of BCAA-containing dipeptides and their intact absorption into circulation to regulate muscle anabolic responses. We investigated the effects of dileucine and leucine ingestion on postprandial muscle protein turnover. Ten healthy young men (age: 23±3 y) consumed either 2 g of leucine (LEU) or 2 g of dileucine (DILEU) in a randomized crossover design. The participants underwent repeated blood and muscle biopsy sampling during primed continuous infusions of L-[ring-13C6]phenylalanine and L-[15N]phenylalanine to determine myofibrillar protein synthesis (MPS) and mixed muscle protein breakdown rates (MPB), respectively. LEU and DILEU similarly increased plasma leucine net area under the curve (AUC; P = 0.396). DILEU increased plasma dileucine AUC to a greater extent than LEU (P = 0.013). Phosphorylation of Akt (P = 0.002), rpS6 (P <0.001) and p70S6K (P < 0.001) increased over time in both LEU and DILEU conditions. Phosphorylation of 4E-BP1 (P = 0.229) and eEF2 (P = 0.999) did not change over time irrespective of condition. Cumulative (0-180 min) MPS increased in DILEU (0.075±0.032 %⋅hour-1), but not in LEU (0.047±0.029 %⋅hour-1; P=0.023). MPB did not differ between LEU (0.043±0.030 %⋅h-1) and DILEU conditions (0.051±0.027 %⋅hour-1; P = 0.659). Our results showed that dileucine ingestion elevated plasma dileucine concentrations and muscle protein turnover by stimulating MPS in young men.

N τ-Methylhistidine Excretion and Myofibrillar Protein Breakdown in Patients Receiving Intravenous or Enteral Nutrition

1980 ◽  
Vol 59 (3) ◽  
pp. 211-214 ◽  
Author(s):  
I. B. Holbrook ◽  
E. Gross ◽  
P. J. Milewski ◽  
K. Shipley ◽  
M. H. Irving
Keyword(s):  
Enteral Nutrition ◽  
Muscle Protein ◽  
Myofibrillar Protein ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Creatinine Excretion ◽  
Non Invasive ◽  
Breakdown Rates ◽  
Invasive Measurement

1. Nτ-Methylhistidine, nitrogen and creatinine were measured in the urine of 10 volunteers on normal and meat-free diets and in 10 vegetarians, and compared with the results from the urine of eight patients with intestinal fistulae on intravenous or enteral nutrition containing no meat. The values obtained were used to calculate fractional breakdown rate of myofibrillar protein. 2. There was a significant fall in the excretion of Nτ-methylhistidine and creatinine and in apparent fractional breakdown rates after 2 days on a meat-free diet. 3. One of the patients had lower, and two of the patients had higher, fractional breakdown rates compared with the vegetarians. 4. Nτ-Methylhistidine and creatinine excretion-5-be a useful and non-invasive measurement of myofibrillar protein degradation in patients on meat-free diets. Firm conclusions cannot, however, be drawn without confirmatory, direct measurement of the breakdown rates of muscle protein in vivo.

Measurement of muscle protein fractional synthesis and breakdown rates from a pulse tracer injection

2002 ◽  
Vol 283 (4) ◽  
pp. E753-E764 ◽  
Author(s):  
Xiao-Jun Zhang ◽  
David L. Chinkes ◽  
Robert R. Wolfe
Keyword(s):  
Muscle Protein ◽  
New Method ◽  
Balance Model ◽  
Synthesis Rate ◽  
Breakdown Rate ◽  
Tracer Injection ◽  
Arterial Blood ◽  
Breakdown Rates ◽  
Fractional Synthesis ◽  
Muscle Biopsies

We have developed a new method to determine the fractional synthesis rate (FSR) and breakdown rate (FBR) of muscle protein. This method involves a pulse tracer injection and measurement of enrichment in the arterial blood and muscle at three time points. The calculations of FSR and FBR are based on the precursor-product principle. To test this method, we gave a pulse injection ofl-[ ring-13C6]phenylalanine of 4–6 mg/kg in five rabbits. The measured FBR value (0.233 ± 0.060%/h) was almost identical ( P = 0.35) to that (0.217 ± 0.078%/h) estimated from a leg arteriovenous balance model (Biolo G, Chinkes D, Zhang X-J, and Wolfe RR. J Parenter Enteral Nutr 16: 305–315, 1992). The measured FSR value tended to be lower than that estimated from the leg model (0.125 ± 0.036 vs. 0.185 ± 0.086%/h; P = 0.14), possibly because the new method measures only muscle FSR, whereas the leg balance model also includes skin and bone contributions. The pulse tracer injection did not affect muscle protein kinetics as measured by leucine and phenylalanine kinetics in the leg. In another five rabbits, we demonstrated that sampling could be reduced to either one or two muscle biopsies when multiple pulse injections were used. This method can be completed in 1 h with one muscle biopsy and has technical advantages over currently used methods.

scholarly journals The effect of intermittent changes in tension on protein and collagen synthesis in isolated rabbit muscles

1981 ◽  
Vol 198 (3) ◽  
pp. 491-498 ◽  
Author(s):  
R M Palmer ◽  
P J Reeds ◽  
G E Lobley ◽  
R H Smith
Keyword(s):  
Protein Synthesis ◽  
Total Protein ◽  
Collagen Synthesis ◽  
Muscle Protein ◽  
Lactate Concentration ◽  
Constant Tension ◽  
Intact Rabbit ◽  
Mechanical Stretching ◽  
Total Muscle

Isolated intact rabbit muscles were incubated in a medium containing radioactive proline. The rates of synthesis of collagen and total muscle protein after incubation with a constant tension or intermittent mechanical stretching were compared with the rates in vivo. Muscles incubated under a constant tension synthesized protein at 22% of the rate observed in vivo; intermittent mechanical stretching resulted in an increase of 73% in the rate of protein synthesis, to 38% of that found in vivo. Collagen synthesis was affected in the same way as total protein synthesis by both types of incubation, therefore the relative rates of collagen and total protein synthesis were unchanged. ATP concentration in the isolate muscles and the uptake of glucose from the medium were increased by intermittent mechanical stretching. Incubating the muscles with a gas phase containing 5% O2 decreased the rate of protein synthesis, abolished the effect of intermittent mechanical stretching, lowered the concentration of ATP and increased the lactate concentration. The rate of protein synthesis in muscles maintained with a constant or intermittently applied tension was not affected by a previous period of incubation with the other type of stimulus.

scholarly journals Assessing the whole-body protein synthetic response to feeding in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Luc J. C. van Loon
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Intake ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein ◽  
Breakdown Rates

All tissues are in a constant state of turnover, with a tightly controlled regulation of protein synthesis and breakdown rates. Due to the relative ease of sampling skeletal muscle tissue, basal muscle protein synthesis rates and the protein synthetic responses to various anabolic stimuli have been well defined in human subjects. In contrast, only limited data are available on tissue protein synthesis rates in other organs. Several organs such as the brain, liver and pancreas, show substantially higher (basal) protein synthesis rates when compared to skeletal muscle tissue. Such data suggest that these tissues may also possess a high level of plasticity. It remains to be determined whether protein synthesis rates in these tissues can be modulated by external stimuli. Whole-body protein synthesis rates are highly responsive to protein intake. As the contribution of muscle protein synthesis rates to whole-body protein synthesis rates is relatively small considering the large amount of muscle mass, this suggests that other organ tissues may also be responsive to (protein) feeding. Whole-body protein synthesis rates in the fasted or fed state can be quantified by measuring plasma amino acid kinetics, although this requires the production of intrinsically labelled protein. Protein intake requirements to maximise whole-body protein synthesis may also be determined by the indicator amino acid oxidation technique, but the technique does not allow the assessment of actual protein synthesis and breakdown rates. Both approaches have several other methodological and inferential limitations that will be discussed in detail in this paper.

scholarly journals Artificial gravity maintains skeletal muscle protein synthesis during 21 days of simulated microgravity

2009 ◽  
Vol 107 (1) ◽  
pp. 34-38 ◽  
Author(s):  
T. B. Symons ◽  
M. Sheffield-Moore ◽  
D. L. Chinkes ◽  
A. A. Ferrando ◽  
D. Paddon-Jones
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Bed Rest ◽  
Artificial Gravity ◽  
Skeletal Muscle Protein ◽  
Longitudinal Loading ◽  
Breakdown Rates

We sought to determine the effects of longitudinal loading (artificial gravity) on skeletal muscle protein kinetics in 15 healthy young males after 21 days of 6° head-down tilt bed rest [experimental treatment (Exp) group: n = 8, 31 ± 1 yr; control (Con) group; n = 7, 28 ± 1 yr, means ± SE]. On days 1 and 21 of bed rest, postabsorptive venous blood samples and muscle biopsies (vastus lateralis and soleus) were obtained during a 1-h pulse bolus infusion protocol (0 min, l-[ ring-13C6]phenylalanine, 35 μmol/kg; 30 min, l-[ ring-15N]phenylalanine, 35 μmol/kg). Outcome measures included mixed muscle fractional synthesis (FSR) and breakdown rates (FBR). The Exp group experienced 1 h of longitudinal loading (2.5G at the feet) via a short-radius centrifuge during each day of bed rest. Mixed muscle FSR in the Con group was reduced by 48.5% ( day 1, 0.081 ± 0.000%/h vs. day 21, 0.042 ± 0.000%/h; P = 0.001) in vastus lateralis after 21 days of bed rest, whereas the Exp group maintained their rate of protein synthesis. A similar but nonsignificant change in FSR was noted for the soleus muscle (Exp, −7%; Con, −22%). No changes in muscle protein breakdown were observed. In conclusion, 1 h of daily exposure to artificial gravity maintained the rate of protein synthesis of the vastus lateralis and may represent an effective adjunct countermeasure to combat the loss of muscle mass and functional during extended spaceflight.

Protein coingestion stimulates muscle protein synthesis during resistance-type exercise

2008 ◽  
Vol 295 (1) ◽  
pp. E70-E77 ◽  
Author(s):  
Milou Beelen ◽  
René Koopman ◽  
Annemie P. Gijsen ◽  
Hanne Vandereyt ◽  
Arie K. Kies ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Protein Hydrolysate ◽  
Muscle Protein Synthesis ◽  
Nutritional Intervention ◽  
Whole Body ◽  
Exercise Session ◽  
Body Protein ◽  
Fed State ◽  
Breakdown Rates

In contrast to the effect of nutritional intervention on postexercise muscle protein synthesis, little is known about the potential to modulate protein synthesis during exercise. This study investigates the effect of protein coingestion with carbohydrate on muscle protein synthesis during resistance-type exercise. Ten healthy males were studied in the evening after they consumed a standardized diet throughout the day. Subjects participated in two experiments in which they ingested either carbohydrate or carbohydrate with protein during a 2-h resistance exercise session. Subjects received a bolus of test drink before and every 15 min during exercise, providing 0.15 g·kg−1·h−1 carbohydrate with (CHO + PRO) or without (CHO) 0.15 g·kg−1·h−1 protein hydrolysate. Continuous intravenous infusions with l-[ ring-13C6]phenylalanine and l-[ ring-2H2]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body and muscle protein synthesis rates during exercise. Protein coingestion lowered whole body protein breakdown rates by 8.4 ± 3.6% ( P = 0.066), compared with the ingestion of carbohydrate only, and augmented protein oxidation and synthesis rates by 77 ± 17 and 33 ± 3%, respectively ( P < 0.01). As a consequence, whole body net protein balance was negative in CHO, whereas a positive net balance was achieved after the CHO + PRO treatment (−4.4 ± 0.3 vs. 16.3 ± 0.4 μmol phenylalanine·kg−1·h−1, respectively; P < 0.01). In accordance, mixed muscle protein fractional synthetic rate was 49 ± 22% higher after protein coingestion (0.088 ± 0.012 and 0.060 ± 0.004%/h in CHO + PRO vs. CHO treatment, respectively; P < 0.05). We conclude that, even in a fed state, protein coingestion stimulates whole body and muscle protein synthesis rates during resistance-type exercise.

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