3-methylhistidine Excretion Research Articles

Effect of five hours of mixed exercise on urinary nitrogen excretion in healthy moderate-to-well-trained young adults.

Carbohydrates and fats are the primary energy substrates during exercise, but proteins can also contribute. When proteins are degraded in the body, the amino groups are mainly converted to urea and excreted. Therefore, nitrogen excretion has been used as a marker of protein degradation, but a clear conclusion has yet to be reached on the effect of exercise on nitrogen excretion. Thus, we tested whether exercise increases nitrogen excretion. Fifteen young, healthy, moderate-to-well-trained participants (4 females, 11 males, VO2max 54.4 ± 1.7 mL·kg-1·min-1; mean ± SEM) participated in a randomized, balanced cross-over design investigation consisting of 1 day with 5 h of exercise (exercise day, EX) and 1 day with no exercise (control day, CON). The participants recorded their dietary intake the day before from 16:00 and throughout the intervention day. They then repeated these dietary intakes on the second trial day. A standardized lunch was provided on both days. In addition, participants were allowed to consume almost protein-free snacks in EX to ensure the same energy balance during both trial days. Urine was collected throughout the whole testing period, and urinary 3-methylhistidine (3-MH) excretion was measured to examine muscular catabolism. The sweat rate was calculated during the exercise period. The urinary nitrogen and 3-MH excretions did not differ significantly between EX and CON (p = 0.764 and p = 0.953). The sweat rate was 2.55 ± 0.25 L in EX and 0.14 ± 0.15 L in CON (p < 0.001), and by estimating sweat nitrogen excretion, total nitrogen excretion was shown to differ with exercise. Our results showed that 5 hours of mixed exercise did not significantly impact urinary nitrogen and 3-MH excretions in healthy moderate-to-well-trained young adults.

Body weight reduction by exercise increases the urinary 3-methylhistidine excretion level with relatively positive nitrogen, sodium, and potassium balances when compared to dietary restriction

BackgroundRegarding changes in muscle mass, differences due to types of exercise and/or nutritional interventions, and associations with nutrient balances are still unclear. MethodsTo estimate changes in muscle mass during a body weight loss program using either a diet or exercise regimen, we investigated levels of muscle mass-related indices, and body contents of nitrogen, sodium, and potassium as measured by the balance method. Six healthy young adult male volunteers participated in two 10-day crossover experiments (20 days total). The first 5 days comprised an adjustment period (energy intake, 2656 ± 367 kcal/day (mean ± standard deviation)). During the second 5-day period, the participants either reduced their energy intake to 1770 ± 244 kcal/day (diet regimen) or exercised on a bicycle ergometer to expend 886 ± 122 kcal/day (exercise regimen). ResultsThe nitrogen, sodium, and potassium balances were significantly more positive during the exercise regimen than during the diet regimen. The urinary excretion levels of creatinine, 3-methylhistidine (3-MH), aldosterone, and catecholamines, and the 3-MH/creatinine ratio were significantly increased only during the exercise regimen. ConclusionsThe exercise regimen suppresses the decrease in muscle mass-related indices during body weight loss compared to the diet regimen with a relatively positive state of whole-body protein, sodium, and potassium balances, accompanied by an increase in sympathetic/adrenal cortical functions.

Carbohydrate Ingestion during Prolonged Cycling Improves Next-Day Time Trial Performance and Alters Amino Acid Concentrations.

Exercise with low carbohydrate availability increases protein degradation, which may reduce subsequent performance considerably. The present study aimed to investigate the effect of carbohydrate ingestion during standardized exercise with and without exhaustion on protein degradation and next-day performance. Seven trained male cyclists (V̇O 2max 66.8 ± 1.9 mL·kg -1 ·min -1 ; mean ± SEM) cycled to exhaustion (~2.5 h) at a power output eliciting 68% of V̇O 2max (W 68% ). This was followed by repeating 1-min work/1-min recovery intervals at 90% of V̇O 2max (W 90% ) until exhaustion. During W 68% , cyclists consumed a placebo water drink (PLA) the first time and a carbohydrate drink (CHO), 1 g carbohydrate·kg -1 ·h -1 , the second time. The participants performed the same amount of work under the two conditions, separated by at least 1 wk. A standardized diet was provided to the participants so that the two conditions were isoenergetic. To test the impact of carbohydrates on recovery, participants completed a time trial (TT) the next day. Carbohydrate ingestion maintained carbohydrate availability during W 68% and W 90% : total carbohydrate oxidation was significantly higher in CHO ( P = 0.022), and plasma glucose concentration was maintained compared with PLA ( P = 0.025). Next-day performance during TT was better after CHO ingestion (CHO, 41:49 ± 1:38 min; PLA, 42:50 ± 1:46 min; P = 0.020; effect size d = 0.23, small), as was gross efficiency (CHO, 18.6% ± 0.3%; PLA, 17.9% ± 0.3%; P = 0.019). Urinary nitrogen excretion ( P = 0.897) and urinary 3-methylhistidine excretion ( P = 0.673) did not significantly differ during the study period. Finally, tyrosine and phenylalanine plasma concentrations increased in PLA but not in CHO ( P = 0.018). Carbohydrate ingestion during exhaustive exercise reduced deterioration in next-day performance through reduced metabolic stress and development of fatigue. In addition, some parameters point toward less protein degradation, which would preserve muscle function.

High Protein Diet Has Beneficial Effects in Murine Muscular Dystrophy

In normal muscle there is a delicate balance between muscle protein synthesis and protein degradation. It is believed that this balance is disturbed in muscular dystrophy (MD) by decreased muscle protein synthesis and/or increased muscle protein degradation, resulting in net catabolism. In an attempt to reduce or reverse this catabolism, a high protein diet (HPD, 50% protein) was fed to dystrophic mice (129/ReJ dy) for 4 wk. The effects on muscle biochemistry, muscle function and muscle morphology were compared with those in dystrophic mice fed a normal diet (NPD, 20% protein) and in nondystrophic mice (NORM) also fed the 20% protein diet. Compared with NORM mice, NPD mice demonstrated greater rates of muscle protein synthesis (P < 0.05) as measured by the incorporation of labeled phenylalanine into muscle, greater protein degradation (P < 0.01) as measured by urinary 3-methylhistidine excretion, and lower muscle protein concentration (P < 0.01). When dystrophic mice were fed HPD for 4 wk, protein degradation was lower (P < 0.01) and muscle protein concentration greater (P < 0.01) than in NPD mice. These biochemical improvements were accompanied by greater morphological uniformity of muscle fibers, higher volume density of muscle fibers per unit area of muscle (P < 0.01), and lower shape factor (P < 0.01). Functionally, HPD led to improved muscle endurance (P < 0.01) and increased hind-limb utilization (P 0.01). We conclude that in murine dystrophy, HPD decreases net muscle catabolism, principally by decreasing muscle protein degradation, resulting in improvement in muscle morphology, strength and function.

Meat intake and risk of mortality and graft failure in kidney transplant recipients

ABSTRACTBackgroundIt is unknown whether meat intake is beneficial for long-term patient and graft survival in kidney transplant recipients (KTR).ObjectivesWe first investigated the association of the previously described meat intake biomarkers 1-methylhistidine and 3-methylhistidine with intake of white and red meat as estimated from a validated food frequency questionnaire (FFQ). Second, we investigated the association of the meat intake biomarkers with long-term outcomes in KTR.MethodsWe measured 24-h urinary excretion of 1-methylhistidine and 3-methylhistidine by validated assays in a cohort of 678 clinically stable KTR. Cross-sectional associations were assessed by linear regression. We used Cox regression analyses to prospectively study associations of log2-transformed biomarkers with mortality and graft failure.ResultsUrinary 1-methylhistidine and 3-methylhistidine excretion values were median: 282; interquartile range (IQR): 132–598 µmol/24 h and median: 231; IQR: 175–306 µmol/24 h, respectively. Urinary 1-methylhistidine was associated with white meat intake [standardized β (st β): 0.20; 95% CI: 0.12, 0.28; P < 0.001], whereas urinary 3-methylhistidine was associated with red meat intake (st β: 0.30; 95% CI: 0.23, 0.38; P < 0.001). During median follow-up for 5.4 (IQR: 4.9–6.1) y, 145 (21%) died and 83 (12%) developed graft failure. Urinary 3-methylhistidine was inversely associated with mortality independently of potential confounders (HR per doubling: 0.55; 95% CI: 0.42, 0.72; P < 0.001). Both urinary 1-methylhistidine and urinary 3-methylhistidine were inversely associated with graft failure independent of potential confounders (HR per doubling: 0.84; 95% CI: 0.73, 0.96; P = 0.01; and 0.59; 95% CI: 0.41, 0.85; P = 0.004, respectively).ConclusionsHigh urinary 3-methylhistidine, reflecting higher red meat intake, is independently associated with lower risk of mortality. High urinary concentrations of both 1- and 3-methylhistidine, of which the former reflects higher white meat intake, are independently associated with lower risk of graft failure in KTR. Future intervention studies are warranted to study the effect of high meat intake on mortality and graft failure in KTR, using these biomarkers.

Immune Status and Growth of Broiler Fed Diet with Microparticle Protein Added with Natural Acidifier

The present study was conducted to evaluate the feeding effect of diet composed of microparticle protein added with lime juice as an acidifier on immune status and efficiency of protein utilization in relation to the growth of broiler chicken. Dietary treatments tested were P1 was diet with 20% intact protein and CaCO3 as a Ca source, P2 was diet with 20% microparticle protein and eggshell as a Ca source added with 1.2% lime juice, and P3 was diet with 20% microparticle protein and eggshell as a Ca source added with 2.4% lime juice. Variables measured were protein and amino acids digestibility, retentions of N and Ca, fecal Nτ–methyl histidine (Nτ–MH) excretion as a protein turnover index, lymphoid organs, heterophil and lymphocyte (H/L) ratio, immunoglobulin A (IgA) as a body resistance indicator, feed consumption, body weight gain (BWG), and feed conversion ratio (FCR). The experiment was arranged in a completely randomized design with 3 treatments and 8 replications. Data were subjected to analysis of variance and Duncan test at 5% probability. Protein and amino acid digestibility, N, and Ca retentions were significantly (p&lt;0.05) higher in P2 and P3. However, the H/L ratio was significantly (p&lt;0.05) lower in both treatments compared to P1. Bursa fabricius and lymph weights were not difference, but BWG in P2 significantly (p&lt;0.05) increased. In conclusion, protein and some essential amino acids digestibility, N and Ca retentions, IgA, and BWG increase with the decrease in H/L ratio, fecal Nτ–MH, feed consumption, and FCR in broiler fed diet composed of microparticle protein source with additional 1.2 mL acidifier of lime juice.

FURTHER STUDIES ON URINARY 3-METHYLHISTIDINE EXCRETION AS AN INDIRECT INDEX OF DIETARY AMINO ACID ADEQUACY IN RATS

As a further step in the determination of the sen­sitivity of urinary 3-methylhistidine (3-MeH) to essential amino acid adequacy in diet, 36 male albino rats of the Wistar strain were divided into six groups +of six rats per group. Each group with an initial .mean live weight of 106.52 ± 0.54g was fed in in­dividual metabolic cages on a basal diet sup­plemented with graded levels of DL-methionine. Total methionine in diet ranged between 0.25 and 1.05%. The study lasted 10 days. The response of urinary 3-methylhistidine excretion to the graded levels of methionine in diet was compared to responses obtained from growth performance characteristics, plasma urea concentration, liver nitrogen and creatinine excretion. With the excep­tion of feed intake, all other indices of dietary pro­tein adequcy and efficient amino acid utilization viz growth rate, protein efficiency ratio, serum urea concentration, and creatinine excretion were significantly (P 0.05) to P 0.01) influenced by dietary methionine level. Maximum growth rate, liver N and urinary 3-methylhistidine were observed. in rats given 0.45% total methionine in diet. Supplementing the basal diet to contain 0.45% total,' methonine significantly (P 0.01) decreased serum urea concentration. Urinary 3-methylhistidlne excre­tion was found by regression analysis to be positively correlated to body weight gain (r = 0.73), feed intake (r = 0.61), urinary creatinine excretion (r = 0.74) and liver N (0.72) but negatively correlated to dietary methionine level (r = —0.41). We suggested that urinary 3-MeH excretion be added to the list of available indicts for dietary amino acid adequacy.

Effects of the amount and frequency of nitrogen supplementation on intake, digestion, and metabolism in cattle fed low-quality tropical grass

This study evaluated the effects of the amount and frequency of N supplementation on intake, digestion, and urinary and blood characteristics in cattle fed low-quality tropical grass hay. Five ruminally and abomasally fistulated crossbred bulls averaging 262 ± 20 kg of body weight were used in a 5 × 5 Latin square design. The basal diet was composed of a low-quality signal grass hay (47.2 g CP/kg DM). Treatments were designed according to a 2 × 2 + 1 factorial arrangement, as follows: supplemented with 30 % of rumen degradable protein (RDP) requirements daily or infrequently every three days; supplemented with 60 % of RDP requirements daily or infrequently every three days; plus a control without supplementation. The N supplement (1,140 g CP/kg DM) was a mixture of casein, urea, and ammonium sulfate. Overall, N supplementation did not affect forage intake when compared to the control. There was an interaction between the amount and frequency of N supplementation on all intake measurements. Infrequent supplementation decreased voluntary intake only when 60 % RDP was infrequently supplied, and this effect was attributed to a decreased intake on the day when supplementation was provided. Supplements generally improved digested organic matter intake but not digested fiber intake, revealing a lack of effects on forage intake and digestion. The N balance and efficiency of N utilization were increased by N supplementation but were not affected by supplementation frequency. Supplementation improved blood IGF-1 but did not affect 3-methylhistidine excretion, indicating a supplemental N effect on muscle anabolism, although it lacked effects on muscle catabolism. Both rumen ammonia-N and serum urea-N were affected by an interaction between treatments and day of supplementation cycle, where variation among days were only observed for infrequent supplementation. The rumen ammonia-N concentration peaked on supplementation day. However, a delay was observed for the peak of serum urea-N, which took place one day after supplementation. This pattern indicates that metabolic mechanisms may contribute to N salvage in animals that are infrequently supplemented. We concluded that infrequent N supplementation does not compromise digestion, N utilization, and metabolism in cattle fed low-quality tropical grass. However, when supplementing with large amounts of N, the infrequent supplementation may negatively affect forage intake.

Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients.

A growing number of patients survive sepsis but remain chronically critically ill. We sought to define clinical outcomes and incidence of chronic critical illness (CCI) after sepsis and to determine whether selected biomarkers of inflammation, immunosuppression, and catabolism differ between these patients and those that rapidly recover (RAP). This 3-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (≥14 days of intensive care unit resource utilization with persistent organ dysfunction). Patient clinical demographics, outcomes, and serial serum/urine samples were collected for plasma protein and urinary metabolite analyses. Of 145 sepsis patients enrolled, 19 (13%) died during their hospitalization and 71 (49%) developed CCI. The CCI patients were significantly older (mean, 63 ± 15 vs. 58 ± 13 years, p = 0.006) and more likely to be discharged to long-term acute care facilities (32% vs. 3%, p < 0.0001), whereas those with RAP were more often discharged to home or a rehabilitation facility. Six-month mortality was significantly higher in CCI as compared with RAP cohort (37% vs. 2%; p < 0.01). Multivariate logistic regression modeling revealed delayed onset sepsis (>48 hours after admission; odds ratio [OR], 10.93; 95% confidence interval [CI], 4.15-28.82]), interfacility transfer (OR, 3.58; 95% CI, 1.43-8.96), vasopressor-dependent septic shock (OR, 3.75; 95% CI, 1.47-9.54), and Sequential Organ Failure Assessment score of 5 or greater at 72 hours (OR, 5.03; 95% CI, 2.00-12.62) as independent risk factors for the development of CCI. The CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles are consistent with persistent immunosuppression (absolute lymphocyte count and soluble programmed death ligand 1) and catabolism (plasma insulin-like growth factor binding protein 3 and urinary 3-methylhistidine excretion). The development of CCI has become the predominant clinical trajectory in critically ill surgical patients with sepsis. These patients exhibit biomarker profiles consistent with an immunocatabolic phenotype of persistent inflammation, immunosuppression, and catabolism. Prognostic, level II.

新生児及び乳児における術後蛋白代謝の研究 : 尿中 3-methylhistidine 排泄量を中心に

新生児及び乳児における術後蛋白代謝の研究 : 尿中 3-methylhistidine 排泄量を中心に

Metabolomic analysis of urine samples of vivax malaria in-patients for biomarker identification

Plasmodium vivax is the most dominating species in the Indian subcontinent among the five Plasmodium species causing malarial infection in humans. This species is generally believed to be benign and classically thought to cause uncomplicated clinical infection that rarely leads to death or other complication. However, recent studies have shown incidences of P. vivax infection leading to severe complications and even death. To understand the biochemical changes at the pathway level and the modality through which the host recovers from the infection, we monitored the small molecular weight metabolites of urine samples of hospital in-patients undergoing treatment for vivax malaria. Metabolomics, involving 1H NMR spectra of urine samples subjected to multivariate statistical analyses, was employed for this purpose. Urine metabolic profiles were used to identify putative biomarkers and establishing correlation with parasite count in the peripheral blood. The untreated malaria patients (day1) exhibited altered excretion of taurine, hippurate, citrate, glycine, 3-methylhistidine and alanine in comparison to the self-control profile on day30. The day1–4 urine metabolite profiles are distinct from day5 and day30 profiles. The latter two profiles are indistinguishable. Temporal trajectories of urinary metabolites indicated an inflection point on day3. The day1 1H NMR profiles, distinct from the profiles of viral fever patients, correlated with the parasitemia levels in the patients and could in fact be used to gauge the anemia status of the patients. This study demonstrates the potential of urine metabolic profiling in understanding the pathophysiology of P. vivax infection and in non-invasive disease diagnosis.

Protein metabolism, feed energy partitioning, behavior patterns and plasma cortisol in Nellore steers with high and low residual feed intake

The objective was to evaluate protein turnover, nitrogen balance, feed energy partitioning, behavior patterns and plasma cortisol in Nellore (B. indicus) cattle with high and low residual feed intake (RFI = actual minus expected dry matter intake). Seventy-two Nellore steers (16 to 21 months-old, 334±19 kg initial body weight) were fed a feedlot diet for 70 days ad libitum. Daily dry matter intake (DMI) and average daily gain (ADG) were recorded individually and RFI was calculated. The 12 steers of lowest (Low-RFI, most efficient) RFI and the 12 ones of highest RFI (High-RFI, least efficient) were evaluated with respect to their behavior patterns and plasma cortisol concentration. Urine was collected for determination of daily 3-methylhistidine excretion (3MH) and myofibrillar protein breakdown rates. Urinary, gaseous and fecal energy losses were determined as well as the N retention and excretion. High-RFI steers tended to have shorter lying and idle periods and greater feeding time and plasma cortisol levels than low-RFI cattle. No RFI effects were seen for urine 3MH excretion and for rates of protein degradation and synthesis. No effects of efficiency class were observed for N excretion or N retention. No RFI effects were observed for dry matter digestibility, digestible energy (DE) and metabolizable energy (ME) content and DE/ME ratio. Methane energy losses were lower for low- compared with high-RFI steers. Protein turnover seems not to affect feed efficiency in Nellore steers. Improved RFI in Nellore steers is probably associated with lower degrees of activity and responsiveness to stress and lower losses of dietary energy as methane.

Metabolic Effects of Intraoperative Amino Acid Infusion in Mongrel Dogs

Background: Intraoperative amino acid infusion can attenuate the decrease in core temperature, but the metabolic effects are uncertain. Methods: Thirty-six healthy mongrel dogs undergoing ileectomy under general anesthesia were infused intraoperatively with normal saline or 18 compound amino acids at 6, 12, and 24 kJ·kg^–1·h^–1 (NS, 6-, 12-, and 24-kJ groups) and studied until 24 h after the operation. Blood glucose, plasma insulin, free fatty acids, and triglyceride concentrations were determined at 7 defined time points. Muscle aminograms, urinary urea, and 3-methylhistidine excretions were measured before and after the operation. Results: Blood glucose and plasma insulin increased amino acid dose dependently during the operation and in the early period after the operation. Free fatty acids were significantly lower in the 12- and 24-kJ groups compared with the NS group at the end of the operation. The negative nitrogen balance was alleviated dose dependently in the amino acid groups on operation day. The urinary 3-methylhistidine decreased significantly during the first 24 h after the operation in the 24-kJ group, while it increased in the other groups with the largest increase in the NS group. Basic, branched-chain, and aromatic amino acids in the vastus lateralis muscle increased dose dependently at the end of the operation in the amino acid groups. Conclusion: Intraoperative amino acid infusion has the dose-dependent effects of increasing blood glucose, inhibiting fat mobilization and muscle protein breakdown.

Protein feeding pattern, casein feeding, or milk-soluble protein feeding did not change the evolution of body composition during a short-term weight loss program

Studies have shown that timing of protein intake, leucine content, and speed of digestion significantly affect postprandial protein utilization. Our aim was to determine if one can spare lean body mass during energy restriction by varying the quality and the timing of protein intake. Obese volunteers followed a 6-wk restricted energy diet. Four groups were compared: casein pulse, casein spread, milk-soluble protein (MSP, = whey) pulse, and MSP spread (n = 10-11 per group). In casein groups, caseins were the only protein source; it was MSP in MSP groups. Proteins were distributed in four meals per day in the proportion 8:80:4:8% in the pulse groups; it was 25:25:25:25% in the spread groups. We measured weight, body composition, nitrogen balance, 3-methylhistidine excretion, perception of hunger, plasma parameters, adipose tissue metabolism, and whole body protein metabolism. Volunteers lost 7.5 ± 0.4 kg of weight, 5.1 ± 0.2 kg of fat, and 2.2 ± 0.2 kg of lean mass, with no difference between groups. In adipose tissue, cell size and mRNA expression of various genes were reduced with no difference between groups. Hunger perception was also never different between groups. In the last week, due to a higher inhibition of protein degradation and despite a lower stimulation of protein synthesis, postprandial balance between whole body protein synthesis and degradation was better with caseins than with MSP. It seems likely that the positive effect of caseins on protein balance occurred only at the end of the experiment.

Molecular characterization of skeletal muscle atrophy in the R6/2 mouse model of Huntington's disease

Huntington's disease (HD), a neurodegenerative disorder caused by mutant huntingtin, is characterized by a catabolic phenotype. To determine the mechanisms underlying muscle wasting, we examined key signal transduction pathways governing muscle protein metabolism, apoptosis, and autophagy in R6/2 mice, a well-characterized transgenic model of HD. R6/2 mice exhibited increased adiposity, elevated energy expenditure, and decreased body weight and lean mass without altered food intake. Severe skeletal muscle wasting accounted for a majority of the weight loss. Protein synthesis was unexpectedly increased 19% in gastrocnemius muscle, which was associated with overactivation of basal and refeeding-stimulated mammalian target of rapamycin (mTOR) signaling, elevated Akt expression and Ser(473) phosphorylation, and decreased AMPK Thr(172) phosphorylation. Moreover, mRNA abundance of atrogenes muscle ring finger-1 and atrophy F-box, was markedly attenuated during fasting and refeeding, and the urinary excretion of 3-methylhistidine was decreased, arguing against a role for the ubiquitin proteasome-mediated proteolysis in the atrophy. In contrast, mRNA expression of several caspase genes and genes involved in the extrinsic or intrinsic apoptotic pathway, caspase-3/7, -8, and -9 activity, protein abundance of caspase-3 and -9, Fas, and Fadd, and cytochrome c release were elevated. Protein expressions of LC3B-I and -II, beclin-I, and atg5 and -7 in muscle were upregulated. Thus, mutant huntingtin in skeletal muscle results in increased protein synthesis and mTOR signaling, which is countered by activation of the apoptotic and autophagic pathways, contributing to an overall catabolic phenotype and the severe muscle wasting.

Molecular Characterization of Skeletal Muscle Atrophy in the R6/2 Mouse Model of Huntington's Disease

Huntington's disease (HD), a neurodegenerative disorder caused by mutant huntingtin, is characterized by a catabolic phenotype. To determine the mechanisms underlying muscle wasting, we examined key signal pathways governing protein metabolism and cellular turnover in R6/2 mice, a well characterized transgenic model of HD. R6/2 exhibited increased adiposity, elevated energy expenditure, decreased body weight and lean mass. Protein synthesis was unexpectedly increased 19% in gastrocnemius muscle, which was associated with overactivation of basal and refeeding-stimulated mTOR signaling, elevated AKT expression and Ser473 phosphorylation, and decreased AMPK Thr172 phosphorylation. Moreover, muscle mRNA expression of atrogenes, ring finger 1 and atrophy F-box was markedly attenuated during fasting and refeeding, and the urinary excretion of 3-methylhistidine was decreased, arguing against a role for the ubiquitin proteasome-mediated proteolysis in the atrophy. In contrast, mRNA expression of genes involved in the extrinsic apoptotic pathway, caspase-3/7, −8 and −9 activity, protein expression of caspase-3 and −9, Fas, and Fadd, and cytochrome C release were elevated. Protein expression of LC3B-I and -II, beclin-I, atg5 and atg7 in muscle was up-regulated. Thus, an increase in apoptosis and autophagy appear to contribute to an overall catabolic phenotype and the severe muscle wasting.

Increased fat-free body mass and no adverse effects on blood lipid concentrations 4 weeks after additional meat consumption in comparison with an exclusion of meat in the diet of young healthy women.

Aims. To investigate whether changes of meat consumption can affect body composition and laboratory parameters in healthy, normal weight, young women without the aim to reduce body weight. Research Design and Methods. Women volunteered to eat low-fat meat in addition to their habitual diet (M) or to exclude meat products from their diet (NOM). After 4 weeks M and NOM were crossed over between subjects. Changes in nutrient intake, morphometrics and plasma parameters were compared during M and NOM. Results. Daily protein intake (means ± SD) was 2.25 ± 0.35 (25.2% of energy) and 1.15 ± 0.26 g/kg (14.0% of energy) during M and NOM, respectively. Fat-free body mass (FFM) increased during M (0.7 ± 1.0 kg, P = .02) and decreased during NOM (−0.8 ± 0.8 kg, P = .003). Body fat mass was unchanged. Concentrations of total cholesterol (−7%), LDL-cholesterol (−8%), and glucose (−4%) deceased significantly after M. Fasting glutamine concentrations were decreased by M and increased by NOM. Conclusions. Additional meat intake can increase FFM without adverse effects on blood lipid concentrations. Long-term studies are required. Urinary excretion of 3-methylhistidine could represent a biomarker for meat protein consumption.

Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue

Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but this atrophy was not associated with reduced basal muscle protein synthesis or differences in plasma IGF-I, insulin, or individual amino acids. However, oral leucine failed to normally stimulate muscle protein synthesis in castrated rats. In addition, castration-induced atrophy was associated with increased 3-methylhistidine excretion and in vitro-determined ubiquitin proteasome activity in skeletal muscle, changes that were associated with decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and kidney weight without reducing protein synthesis and did not alter either cardiac output or glomerular filtration. In contradistinction, the weight of the retroperitoneal fat depot was increased in castrated rats. This increase was associated with an elevated rate of basal protein synthesis, which was unresponsive to leucine stimulation. Castration also decreased whole body fat oxidation. Castration increased TNFα, IL-1α, IL-6, and NOS2 mRNA in fat but not muscle. In summary, the castration-induced muscle wasting results from an increased muscle protein breakdown and the inability of leucine to stimulate protein synthesis, whereas the expansion of the retroperitoneal fat depot appears mediated in part by an increased basal rate of protein synthesis-associated increased inflammatory cytokine expression.

3-Methyl Histidine Excretion in Starvation.

Urinary excretion of 3-methyl histidine was found to be reduced in starvation. Data show that the rate of muscle catabolism is reduced to a greater extent than muscle mass. Reutilization of amino acids appears not to be greatly enhanced during starvation.

Glucose Infusion Suppresses Surgery-induced Muscle Protein Breakdown by Inhibiting Ubiquitin-proteasome Pathway in Rats

It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in the early postoperative period, the effects of surgical stress and glucose infusion on muscle protein catabolism and the related mechanisms remain unclear. Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml x kg(-1) x h(-1)) without glucose (control) or containing 1% or 5% glucose. The infusion was continued for a further 4 h after the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3-methylhistidine, and release of tyrosine and 3-methylhistidine from isolated muscle were determined. Furthermore, muscular mRNA expression of proteolytic-related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and cathepsin L and H) and phosphorylation of components of insulin signaling (forkhead box O3 and protein kinase B) were evaluated. Surgery increased the catabolic index, and this increase was suppressed by glucose infusion (both 1% and 5%). In the control group, mRNA expression of atrogin-1/MAFbx and muscle ring finger-1 was increased, and they were suppressed in the two glucose groups. Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead box O3) in muscles was stimulated by glucose infusion. The present study indicates that glucose infusion, even at a relatively low rate, suppresses muscle protein breakdown in the early postoperative period. The mechanism of this effect is related to the suppression of the ubiquitin-proteasome pathway, accompanied by activation of insulin signaling.