Depression of Muscle Protein Synthesis (MPS) with no Evidence of Elevated Muscle Protein Breakdown (MPB) Precedes Minor Muscle Wasting in Early Colorectal Cancer

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.

Download Full-text

Muscle Protein Metabolism in the Elderly: Influence of Exercise and Nutrition

Canadian Journal of Applied Physiology ◽

10.1139/h01-033 ◽

2001 ◽

Vol 26 (6) ◽

pp. 588-606 ◽

Cited By ~ 18

Author(s):

Kevin D. Tipton

Keyword(s):

Protein Synthesis ◽

Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Effective Means ◽

The Elderly ◽

Protein Breakdown ◽

Small Magnitude ◽

Muscle Protein Breakdown ◽

Metabolic Basis

Although the causes of sarcopenia are multi-factorial, at least some, such as poor nutrition and inactivity, may be preventable. Changes in muscle mass must be a result of net muscle protein breakdown over that particular time period. Stable isotope methodology has been used to examine the metabolic basis of muscle loss. Net muscle protein breakdown may occur due to a decrease in the basal level of muscle protein synthesis. However, changes of this type would likely be of small magnitude and undetectable by current methodology. Hormonal mediators may also be important, especially in association with forced inactivity. Net muscle protein breakdown may be also attributed to alterations in the periods of net muscle protein synthesis and breakdown each day. Reduced activity, combined with ineffectual nutrient intake, could lead to decreased net muscle protein balance. Chronic resistance exercise training clearly is an effective means of increasing muscle mass and strength in elderly individuals. Although sometimes limited, acute metabolic studies provide valuable information for maintenance of muscle mass with age. Key words: sarcopenia, inactivity, strength training, muscle protein synthesis, muscle hypertrophy

Download Full-text

Effect of heart failure on the regulation of skeletal muscle protein synthesis, breakdown, and apoptosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00517.2002 ◽

2003 ◽

Vol 284 (5) ◽

pp. E1001-E1008 ◽

Cited By ~ 15

Author(s):

Rebecca Persinger ◽

Yvonne Janssen-Heininger ◽

Simon S. Wing ◽

Dwight E. Matthews ◽

Martin M. LeWinter ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Protein Synthesis ◽

Food Intake ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis

Heart failure is often characterized by skeletal muscle atrophy. The mechanisms underlying muscle wasting, however, are not fully understood. We studied 30 Dahl salt-sensitive rats (10 male, 20 female) fed either a high-salt (HS; n = 15) or a low-salt (LS; n = 15) diet. This strain develops cardiac hypertrophy and failure when fed a HS diet. LS controls were matched to HS rats for gender and duration of diet. Body mass, food intake, and muscle mass and composition were measured. Skeletal muscle protein synthesis was measured by isotope dilution. An additional group of 27 rats (HS, n = 16; LS; n = 11) were assessed for expression of genes regulating protein breakdown and apoptosis. Gastrocnemius and plantaris muscles weighed less (16 and 22%, respectively) in HS than in LS rats ( P < 0.01). No differences in soleus or tibialis anterior weights were found. Differences in muscle mass were abolished after data were expressed relative to body size, because HS rats tended ( P = 0.094) to weigh less. Lower body mass in HS rats was related to a 16% reduction ( P < 0.01) in food intake. No differences in muscle protein or DNA content, the protein-to-DNA ratio, or muscle protein synthesis were found. Finally, no differences in skeletal muscle gene expression were found to suggest increased protein breakdown or apoptosis in HS rats. Our results suggest that muscle wasting in this model of heart failure is not associated with alterations in skeletal muscle metabolism. Instead, muscle atrophy was related to reduced body weight secondary to decreased food intake. These findings argue against the notion that heart failure is characterized by a skeletal muscle myopathy that predisposes to atrophy.

Download Full-text

Muscle wasting in emphysema

Clinical Science ◽

10.1042/cs0750415 ◽

1988 ◽

Vol 75 (4) ◽

pp. 415-420 ◽

Cited By ~ 73

Author(s):

W. L. Morrison ◽

J. N. A. Gibson ◽

C. Scrimgeour ◽

M. J. Rennie

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Myofibrillar Protein ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Download Full-text

Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a ‘Combined Oral Stable Isotope Assessment of Muscle (COSIAM)’ approach

GeroScience ◽

10.1007/s11357-021-00386-2 ◽

2021 ◽

Author(s):

Jessica Cegielski ◽

Daniel J. Wilkinson ◽

Matthew S. Brook ◽

Catherine Boereboom ◽

Bethan E. Phillips ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Stable Isotope ◽

Muscle Mass ◽

Protein Turnover ◽

Skeletal Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Muscle Protein Breakdown

AbstractOptimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits the applicability of these approaches in certain populations (e.g. clinical, frail elderly). To concurrently quantify skeletal muscle mass and muscle protein turnover i.e. muscle protein synthesis (MPS) and muscle protein breakdown (MPB), in elderly human volunteers using stable-isotope labelled tracers i.e. Methyl-[D3]-creatine (D3-Cr), deuterium oxide (D2O), and Methyl-[D3]-3-methylhistidine (D3-3MH), to measure muscle mass, MPS and MPB, respectively. We recruited 10 older males (71 ± 4 y, BMI: 25 ± 4 kg.m2, mean ± SD) into a 4-day study, with DXA and consumption of D2O and D3-Cr tracers on day 1. D3-3MH was consumed on day 3, 24 h prior to returning to the lab. From urine, saliva and blood samples, and a single muscle biopsy (vastus lateralis), we determined muscle mass, MPS and MPB. D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r = 0.69, P = 0.027). Rates of cumulative myofibrillar MPS over 3 days were 0.072%/h (95% CI, 0.064 to 0.081%/h). Whole-body MPB over 6 h was 0.052 (95% CI, 0.038 to 0.067). These rates were similar to previous literature. We demonstrate the potential for D3-Cr to be used alongside D2O and D3-3MH for concurrent measurement of muscle mass, MPS, and MPB using a minimally invasive design, applicable for clinical and frail populations.

Download Full-text

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00599.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. E1534-E1542 ◽

Cited By ~ 22

Author(s):

Dominic S. C. Raj ◽

Oladipo Adeniyi ◽

Elizabeth A. Dominic ◽

Michel A. Boivin ◽

Sandra McClelland ◽

...

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Protein Catabolism ◽

Acid Infusion ◽

Amino Acid Infusion ◽

Muscle Protein Breakdown

Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol·min−1·100 ml −1) was more negative during HD-O compared with pre-HD (−33.7 ± 1.5 vs. −6.0 ± 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (−16.9 ± 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively ( P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

Download Full-text

The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass

Biochemical Journal ◽

10.1042/bj1560185 ◽

1976 ◽

Vol 156 (1) ◽

pp. 185-188 ◽

Cited By ~ 224

Author(s):

D J Millward ◽

P J Garlick ◽

D O Nnanyelugo ◽

J C Waterlow

Keyword(s):

Protein Synthesis ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Relative Importance ◽

Protein Breakdown ◽

Protein Mass ◽

Branched Chain ◽

Amino Acid Concentrations

The effects of growth-suppressing and muscle-wasting treatments on muscle protein turnover and amino acid concentrations were determined in vivo. All treatments depressed protein synthesis and some treatments depressed protein breakdown. Only prolonged starvation increased protein breakdown. Muscle protein mass is regulated primarily through alterations in protein synthesis in all except emergency conditions. The increased concentrations of the branched-chain amino acids indicate that they are unlikely to be involved in this regulation.

Download Full-text

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00170.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. E999-E1006 ◽

Cited By ~ 42

Author(s):

Jill A. Bell ◽

Satoshi Fujita ◽

Elena Volpi ◽

Jerson G. Cadenas ◽

Blake B. Rasmussen

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Insulin Infusion ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Short Term ◽

Muscle Protein Breakdown ◽

Amino Acid Availability ◽

Leg Muscle

Muscle protein synthesis requires energy and amino acids to proceed and can be stimulated by insulin under certain circumstances. We hypothesized that short-term provision of insulin and nutritional energy would stimulate muscle protein synthesis in healthy subjects only if amino acid availability did not decrease. Using stable isotope techniques, we compared the effects on muscle phenylalanine kinetics across the leg of an amino acid-lowering, high-energy (HE, n = 6, 162 ± 20 kcal/h) hyperglycemic hyperlipidemic hyperinsulinemic clamp with systemic insulin infusion to a low-energy (LE, n = 6, 35 ± 3 kcal/h, P < 0.05 vs. HE) euglycemic hyperinsulinemic clamp with local insulin infusion in the femoral artery. Basal blood phenylalanine concentrations and phenylalanine net balance, muscle protein breakdown, and synthesis (nmol·min−1·100 g leg muscle−1) were not different between groups. During insulin infusion, femoral insulinemia increased to a similar extent between groups and blood phenylalanine concentration decreased 27 ± 3% in the HE group but only 9 ± 2% in the LE group ( P < 0.01 HE vs. LE). Phenylalanine net balance increased in both groups, but the change was greater ( P < 0.05) in the LE group. Muscle protein breakdown decreased in the HE group (58 ± 12 to 35 ± 7 nmol·min−1·100 g leg muscle−1) and did not change in the LE group. Muscle protein synthesis was unchanged in the HE group (39 ± 6 to 30 ± 7 nmol·min−1·100 g leg muscle−1) and increased ( P < 0.05) in the LE group (41 ± 9 to 114 ± 26 nmol·min−1·100 g leg muscle−1). We conclude that amino acid availability is an important factor in the regulation of muscle protein synthesis in response to insulin, as decreased blood amino acid concentrations override the positive effect of insulin on muscle protein synthesis even if excess energy is provided.

Download Full-text

Control of Muscle Protein Breakdown: Effects of Activity and Nutritional States

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.11.s1.s164 ◽

2001 ◽

Vol 11 (s1) ◽

pp. S164-S169 ◽

Cited By ~ 17

Author(s):

Robert R. Wolfe

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Human Subjects ◽

Physiological State ◽

Essential Amino Acids ◽

Protein Breakdown ◽

Muscle Protein Breakdown ◽

Prevailing Rate ◽

Stimulation Of

We propose that there is a link between muscle protein synthesis and breakdown that is regulated, in part, through maintenance of the free intracellular pool of essential amino acids. For example, we propose that muscle protein breakdown is paradoxically elevated in the anabolic state following resistance exercise in part because the even greater stimulation of synthesis would otherwise deplete this pool. Thus, factors regulating muscle protein breakdown must be evaluated in the context of the prevailing rate of muscle protein synthesis. Further, the direct effect of factors on breakdown may depend on the physiological state. For example, local hyperinsulinemia suppresses accelerated muscle protein breakdown after exercise, but not normal resting breakdown. Thus, factors regulating muscle protein breakdown in human subjects are complex and interactive.

Download Full-text

Exercise, Protein Metabolism, and Muscle Growth

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.11.1.109 ◽

2001 ◽

Vol 11 (1) ◽

pp. 109-132 ◽

Cited By ~ 107

Author(s):

Kevin D. Tipton ◽

Robert R. Wolfe

Keyword(s):

Protein Synthesis ◽

Protein Metabolism ◽

Muscle Hypertrophy ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Muscle Growth ◽

Protein Breakdown ◽

Muscle Protein Breakdown ◽

Amino Acid Availability ◽

Muscle Protein Metabolism

Exercise has a profound effect on muscle growth, which can occur only if muscle protein synthesis exceeds muscle protein breakdown; there must be a positive muscle protein balance. Resistance exercise improves muscle protein balance, but, in the absence of food intake, the balance remains negative (i.e., catabolic). The response of muscle protein metabolism to a resistance exercise bout lasts for 24-48 hours; thus, the interaction between protein metabolism and any meals consumed in this period will determine the impact of the diet on muscle hypertrophy. Amino acid availability is an important regulator of muscle protein metabolism. The interaction of postexercise metabolic processes and increased amino acid availability maximizes the stimulation of muscle protein synthesis and results in even greater muscle anabolism than when dietary amino acids are not present. Hormones, especially insulin and testosterone, have important roles as regulators of muscle protein synthesis and muscle hypertrophy. Following exercise, insulin has only a permissive role on muscle protein synthesis, but it appears to inhibit the increase in muscle protein breakdown. Ingestion of only small amounts of amino acids, combined with carbohydrates, can transiently increase muscle protein anabolism, but it has yet to be determined if these transient responses translate into an appreciable increase in muscle mass over a prolonged training period.

Download Full-text