Total Branched-chain Amino Acids Research Articles

Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes

Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-α [TNF-α]) concentrations, and an updated homeostasis model assessment of insulin resistance (HOMA2-IR) were measured. The association between the concentrations of total BCAAs and adipokines was adjusted for confounding factors, including body mass index. For the lowest and highest BCAA quartiles, the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51 and 0.91 μg/mL, in men (P for trend < 0.0001); 3.61 and 2.29 μg/mL, in women (P = 0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620 pg/mL, in men (P = 0.003), and 4270 and 6510 pg/mL, in women (P = 0.003). Those for HOMA2-IR were 0.89 and 1.11, in men (P < 0.0001), and 0.79 and 0.96, in women (P < 0.0001); no significant association was found with TNF-α. These results suggest significant associations between BCAA concentrations and those for adiponectin, leptin and HOMA2-IR in individuals without diabetes.

Circulating branched-chain amino acids in children with obstructive sleep apnea

The effects of obstructive sleep apnea (OSA) on the metabolic system are not well understood, especially in children. Recent studies have provided evidence of the modulation of insulin action by branched-chain amino acids (BCAAs) and suggested novel mechanistic relationships between glucose and amino acid metabolic pathways. We hypothesized that plasma BCAA levels may serve as biomarkers of insulin resistance and metabolic dysfunction in children with OSA. A polysomnography was conducted for the diagnosis of OSA in 90 snoring children, in a tertiary hospital. Anthropometric and clinical data were measured and venous blood samples were collected for the measurement of plasma glucose, insulin, HbA1c, and amino acids. Children with OSA had significantly higher levels of BCAAs (leucine, isoleucine, and total BCAAs) compared with those without OSA (P = 0.024). A positive significant correlation was observed between insulin levels and both leucine and isoleucine (r = 0.232; P < 0.05). On multivariate regression analyses, the presence of OSA was significantly associated with leucine, isoleucine, and total BCAA concentrations (P = 0.028), whereas the arousal index was associated with leucine, valine, and total BCAA levels (P = 0.037). The presence of OSA and sleep fragmentation may induce changes in branched-chain amino acid metabolism in snoring children, independently of obesity. These data may suggest a new mechanism linking OSA and glucose homeostasis.

Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women's Health Initiative.

Knowledge regarding association of dietary branched-chain amino acid (BCAA) and type 2 diabetes (T2D), and the contribution of BCAA from meat to the risk of T2D are scarce. We evaluated associations between dietary BCAA intake, meat intake, interaction between BCAA and meat intake and risk of T2D. Data analyses were performed for 74 155 participants aged 50-79 years at baseline from the Women's Health Initiative for up to 15 years of follow-up. We excluded from analysis participants with treated T2D, and factors potentially associated with T2D or missing covariate data. The BCAA and total meat intake was estimated from FFQ. Using Cox proportional hazards models, we assessed the relationship between BCAA intake, meat intake, and T2D, adjusting for confounders. A 20 % increment in total BCAA intake (g/d and %energy) was associated with a 7 % higher risk for T2D (hazard ratio (HR) 1·07; 95 % CI 1·05, 1·09). For total meat intake, a 20 % increment was associated with a 4 % higher risk of T2D (HR 1·04; 95 % CI 1·03, 1·05). The associations between BCAA intake and T2D were attenuated but remained significant after adjustment for total meat intake. These relations did not materially differ with or without adjustment for BMI. Our results suggest that dietary BCAA and meat intake are positively associated with T2D among postmenopausal women. The association of BCAA and diabetes risk was attenuated but remained positive after adjustment for meat intake suggesting that BCAA intake in part but not in full is contributing to the association of meat with T2D risk.

Dietary BCAA Intake Is Associated with Demographic, Socioeconomic and Lifestyle Factors in Residents of São Paulo, Brazil.

Background: Identifying which risk groups have a higher intake of branched chain amino acids (BCAA) is important for the planning of public policies. This study was undertaken to investigate BCAA consumption, the foods contributing to that consumption and their association with demographic, socioeconomic and lifestyle factors. Methods: Data from the Health Survey of São Paulo, a cross-sectional population-based survey (n = 1662; age range 12–97 years), were used. Dietary intake was measured using 24-h dietary recalls. Baseline characteristics were collected. Associations between BCAA intake and demographic, socioeconomic and lifestyle factors were determined using linear regression. Results: Total BCAA intake was 217.14 mg/kg·day (Leu: 97.16 mg/kg·day; Ile: 56.44 mg/kg·day; Val: 63.54 mg/kg·day). BCAA intake was negatively associated with female sex in adolescents and adult groups, with no white race in adolescents, and with former smoker status in adults. Conversely, BCAA was positively associated with household per capita income in adolescents and adults. No associations were observed in the older adults group. Main food contributors to BCAA were unprocessed red meat, unprocessed poultry, bread and toast, beans and rice. Conclusions: Adolescents and adults were the most vulnerable to having their BCCA intake influenced by demographic, socioeconomic and lifestyle factors.

Association of plasma concentrations of branched-chain amino acids with risk of colorectal adenoma in a large Japanese population

Available evidence from animal studies suggests that branched-chain amino acids (BCAAs) may have a protective effect against colorectal carcinogenesis. However, a possible effect of BCAAs against colorectal neoplasia has not been evaluated in humans. Here, we aimed to evaluate whether plasma concentrations of BCAA are associated with the risk of colorectal adenoma (CRA), a precursor lesion of colorectal cancer. CRA cases and controls were identified from examinees who underwent total colonoscopy as part of a cancer screening program between 2004 and 2005 and responded to self-administered dietary and lifestyle questionnaires. We measured plasma concentrations of leucine, isoleucine and valine in 629 patients with adenoma and 584 controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between BCAA and CRA risk after adjustment for potential confounders. High plasma concentrations of leucine, valine and total BCAA were inversely associated with CRA risk after adjustment of potential confounders. The multivariate-adjusted ORs for the highest versus lowest quartiles were 0.60 (95% CI 0.42-0.87, Ptrend = 0.006) for leucine, 0.68 (95% CI 0.48-0.97, Ptrend = 0.09) for valine and 0.68 (95% CI 0.48-0.98, Ptrend = 0.10) for total BCAA. Further analysis by gender revealed that this inverse association was clearly evident in men, but not in women: the corresponding OR for leucine, valine and total BCAA was 0.50 (95% CI 0.32-0.80, Ptrend = 0.003), 0.60 (95% CI 0.38-0.95, Ptrend = 0.01) and 0.58 (95% CI 0.37-0.93, Ptrend = 0.04), respectively, in men and 0.78 (95% CI 0.42-1.45, Ptrend = 0.44), 0.77 (95% CI 0.41-1.43, Ptrend = 0.85) and 0.84 (95% CI 0.45-1.57, Ptrend = 0.81), respectively, in women. Our finding suggests that BCAAs may have a beneficial influence against the process of colorectal carcinogenesis, at least in the early stage. The mechanisms underlying this potential association between BCAA and colorectal carcinogenesis warrant further investigation.

Muscle Protein Signaling in C2C12 Cells Is Stimulated to Similar Degrees by Diverse Commercial Food Protein Sources and Experimental Soy Protein Hydrolysates.

Dietary protein stimulates muscle protein synthesis and is essential for muscle health. We developed a screening assay using C2C12 mouse muscle cells to assess the relative abilities of diverse commercial protein sources and experimental soy protein hydrolysates (ESH), after simulated gut digestion (SGD), to activate the mechanistic target of rapamycin complex I (mTORC1) muscle protein synthesis signaling pathway (p70S6K(Thr389) phosphorylation). Activation of mTORC1 was expressed as a percentage of a maximal insulin response. The bioactivities of proteins grouped by source including fish (81.3 ± 10.6%), soy (66.2 ± 4.7%), dairy (61.8 ± 4.3%), beef (53.7 ± 8.6%), egg (52.3 ± 10.6%), soy whey (43.4 ± 8.6%), and pea (31.4 ± 10.6%) were not significantly different from each other. Bioactivity for ESH ranged from 28.0 ± 7.5 to 98.2 ± 6.6%. The results indicate that both the protein source and processing conditions are key determinants for mTORC1 activation. Regression analyses demonstrated that neither leucine nor total branched-chain amino acid content of proteins is the sole predictor of mTORC1 activity and that additional factors are necessary.

The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population.

BackgroundIt has been suggested that serum branched-chain amino acids (BCAAs) are associated with the incident, progression and prognostic of type 2 diabetes. However, the role of BCAAs in metabolic dyslipidemia (raised triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C)) remains poorly understood. This study aims to investigate 1) the association of serum BCAAs with total cholesterol (TC), TG, HDL-C and low-density lipoprotein cholesterol (LDL-C) and 2) the association between serum BCAAs levels and risk of metabolic dyslipidemia in a community population with different glucose homeostasis.MethodsDemographics data and blood samples were collected from 2251 Chinese subjects from the Huaian Diabetes Protective Program (HADPP) study. After exclusion for cardiovascular disease (CVD), serious hepatic or nephritic diseases and others, 1320 subjects remained for analysis (789 subjects with hemoglobin A1c (HbA1c) > 5.7, 521 with HbA1c ≤ 5.7). Serum BCAAs level was measured by liquid chromatography-tandem mass spectrometry (LC MS/MS). The association of BCAAs with lipids or with the risk of metabolic dyslipidemia was analyzed.ResultsElevated serum BCAAs (both total and individual BCAA) were positively associated with TG and inversely associated with HDL-C in the whole population. These correlations were still significant even after adjustment for confounding factors (r = 0.165, p < 0.001 for TG; and r = -0.126, p < 0.001 for HDL-C). For reduced HDL-C, we found higher odds risk (OR) of Valine (Val) in high HbA1c group than in the low one (OR = 1.055, p < 0.001 vs OR = 1.032, p = 0.059). Compared with that in the first quartile, the multivariable-adjusted OR (95 % CI) of the 4th quartile of serum total BCAAs level for reduced HDL-C was 3.689 (2.325, 5.854) in high HbA1c group and 2.329 (1.284, 4.227) in low group, for raised TG was 3.305 (2.120, 5.152) and 2.972 (1.706, 5.176), and for metabolic dyslipidemia was 3.703 (2.261, 6.065) and 3.702 (1.877, 7.304), respectively (all p < 0.01).ConclusionElevated serum BCAAs level are positively associated with incident metabolic dyslipidemia. In addition, glucose homeostasis could play a certain role in BCAAs-related dyslipidemia.

Lactation is associated with altered metabolomic signatures in women with gestational diabetes.

Lactation for >3months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3months is associated with altered metabolomic signatures postpartum. We enrolled 197 women with gestational diabetes at a median of 3.6years (interquartile range 0.7-6.5years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3months and women who lactated for ≤3months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks. Lactation for >3months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branched-chain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3months and have been linked to the pathophysiology of type 2 diabetes in previous studies. Lactation for >3months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes.

Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects.

Aims/IntroductionElevation of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine, has been observed in obesity-related insulin resistance. However, there have been few studies on Asians, who are generally less obese and less insulin-resistant than Caucasian or African-Americans. In the present study, we investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) and plasma amino acid concentration in non-diabetic Japanese participants.Materials and MethodsA total of 94 healthy men and women were enrolled, and plasma amino acid concentration was measured by liquid chromatography/mass spectrometry after overnight fasting. The associations between HOMA-IR and 20 amino acid concentrations, and anthropometric and clinical parameters of lifestyle-related diseases were evaluated.ResultsThe mean age and body mass index were 40.1 ± 9.6 years and 22.7 ± 3.9, respectively. Significantly positive correlations were observed between HOMA-IR and valine, isoleucine, leucine, tyrosine, phenylalanine and total BCAA concentration. Compared with the HOMA-IR ≤ 1.6 group, the HOMA-IR > 1.6 group showed significantly exacerbated anthropometric and clinical parameters, and significantly elevated levels of valine, isoleucine, leucine, tyrosine, phenylalanine and BCAA.ConclusionsThe present study shows that the insulin resistance-related change in amino acid profile is also observed in non-diabetic Japanese subjects. These amino acids include BCAAs (valine, isoleucine and leucine) and aromatic amino acids (tyrosine and phenylalanine), in agreement with previous studies carried out using different ethnic groups with different degrees of obesity and insulin resistance.

Creatine Supplementation Increases Muscle Branched‐Chain Amino Acids in an Alzheimer Mouse Model

Besides mental dysfunctions, Alzheimer's disease (AD) may impair muscle function. Creatine supplementation (CR) can enhance skeletal muscle mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. We examined the effect of oral CR on muscle amino acids (AA) level in an AD model.24 triple transgenic (3×Tg, ~8 mo old) AD mice were randomly assigned to control (CON; 6 males (M)/6 females (F)) or CR (3% w/w; 4M/8F) diet. Bodyweights and feed intakes were measured throughout the 8‐week study. Quadriceps muscle (QM) was collected at the end to analyze for levels of creatine and AA and measured by high‐performance liquid‐chromatography. Data (mean±SEM) were analyzed by 2‐way ANOVAs.Feed intakes and changes in bodyweight were similar among groups (p&gt;0.05). Creatine content in QM was higher (p=0.067) in CR (M: 0.38±0.04, F: 0.38±0.02 nmol/μl) vs. CON (M: 0.33±0.01, F: 0.35±0.01 nmol/μl). Total branched‐chain AA (BCAA) level in QM was greater for CR (M: 111.10±8.51, F: 87.26±4.31 nmol/mg tissue) vs. CON (M: 78.56±4.46, F: 66.07±4.35 nmol/mg tissue). BCAA/non‐BCAA ratio was higher (p=0.002) in CR (M: 0.87±0.17, F: 0.58±0.03) vs. CON (M: 0.54±0.04, F: 0.45±0.03). Particularly, leucine was dramatically increased (p&lt;0.0001) in CR (M: 61.15±5.64, F: 47.28±2.55 nmol/mg) vs. CON (M: 34.21±2.64, F: 25.49±2.38 nmol/mg).CR supplementation enhances muscle AA contents, increasing BCAA levels in the 3×Tg AD mouse model, which may promote muscle function in AD.Funded by CIHR and Everett Endowment Fund

Growth and nutritional status of children with maple syrup urine disease (MSUD)

Purpose – The purpose of this paper is a single-center six-month follow-up study to determine nutritional status of children with maple syrup urine disease (MSUD). Prolonged restriction on essential amino acid could cause malnutrition. By far, there is no study reported in the context of nutritional status among children with maple syrup urine disease (MSUD), who required life-long protein restriction. Design/methodology/approach – A total of 22 children with MSUD, aged from 1 to 12 years (6.54 ± 3.27) undergoing regular treatment in Institute of Pediatrics, Hospital Kuala Lumpur, were recruited. Body height, weight and head circumference were measured for anthropometry, whereas total protein, albumin and plasma branched-chain amino acid were measured for biochemical aspects. Clinical features diagnosed by pediatrician were recorded from children’s medical record. The 24-hour dietary recall was conducted to measure their nutrients intake. All assessments were repeated at six-month interval except clinical profile. Findings – There were no significant differences in all nutritional parameters from baseline to end of the visit. There was a prominence (particular noticeable of) of growth stunting (68; 64 per cent), undernutrition (35; 32 per cent) and microcephalic (57; 57 per cent) among children with MSUD. Nevertheless, children showed no significant improvement of anthropometric variables from baseline and after 6-month follow-up visit. Nearly all biochemical indicators were significantly (p &lt; 0.05) higher than the reference value except valine. Intellectual disability was the most frequently (71 per cent) presenting symptoms among them. The finding also did not show any macro- or micronutrients fail to achieve above recommended nutrient intake in both visits. In conclusion, it is clear that no significant nutritional deficiency was induced by the use of MSUD dietary therapy; however, the findings indicated that MSUD children are at risk of malnutrition and regular nutritional assessment and monitoring should always be emphasized for optimal linear growth without affecting their amino acid profiles. Research limitations/implications – Multiple 24-hour recalls instead of single 24-hour recall should be used in this study for a better estimate of intake. Originality/value – Although there are retrospective studies targeted in presenting the clinical and biochemical profile of MSUD children which has been extensively examined, limited research has focused on prospective aspect of nutritional status of these children who are undergoing active and regular diet and medical nutrition therapy because of the absence of comprehensive reliable nutritional assessment data.

Effects of supplementation with branched chain amino acids and ornithine aspartate on plasma ammonia and central fatigue during exercise in healthy men.

Our previous studies showed only slight improvement in central fatigue, measured indirectly by psychomotor performance, after branched chain amino acids (BCAA) supplementation during various efforts in healthy men. It is hypothesised that hyperammonaemia resulting from amino acids metabolism may attenuate their beneficial effect on psychomotor performance; therefore, the L-ornithine L-aspartate (OA) as an ammonia decreasing agent was used. The aim of this study was to investigate the effectiveness of oral BCAA + OA supplementation to reduce plasma ammonia concentration and enhance psychomotor performance during exhaustive exercise in healthy men. Eleven endurance-trained men (mean age 32.6 ± 1.9 years) performed two sessions (separated by one week) of submaximal cycloergometer exercise for 90 minutes at 60% of maximal oxygen uptake followed by graded exercise until exhaustion with randomised, double-blind supplementation with a total of 16 g BCAA and 12 g OA (BCAA + OA trial) or flavoured water (placebo trial). Before exercise, during both efforts and after 20 minutes of recovery multiple choice reaction time (MCRT), perceived exertion, heart rate and oxygen uptake were measured and venous blood samples were taken for plasma leucine, valine, isoleucine, ornithine, aspartate, free tryptophan (fTRP), ammonia, lactate and glucose determination. After ingestion, during both efforts and after 20 minutes of recovery the plasma concentrations of all supplemented amino acids were significantly increased, while the fTRP/BCAA ratio decreased in the BCAA + OA trial more than in the placebo trial. At the end of graded exercise plasma fTRP was lower and MCRT shorter in BCAA + OA than in the placebo trial (p < 0.05). At the end of prolonged exercise the plasma ammonia concentration was higher in BCAA + OA than in placebo trial (p < 0.05). Decreases in plasma ammonia during recovery were significantly higher in BCAA + OA than in the placebo trial. Plasma ammonia positively correlated with the total plasma BCAA and MCRT only in the BCAA + OA trial. The fTRP/BCAA ratio positively correlated with MCRT only in the placebo trial. Supplementation with BCAA and OA is a useful way to improve MCRT during high-intensity exercise and accelerate the elimination of ammonia at the recovery stage after exercise in healthy young men.

Dietary branched-chain amino acid supplementation affects growth and hepatic insulin-like growth factor gene expression in yellowtail,Seriola quinqueradiata

We investigated the effect of dietary supplementation with a branched-chain amino acid (BCAA) mixture (valine, leucine and isoleucine) on juvenile yellowtail (Seriola quinqueradiata) growth and hepatic insulin-like growth factor (IGF) gene expression. Total dietary BCAA content was 8.1, 8.5, 9.0 and 9.8 g kg−1 for the control, 0.4%, 1.0% and 2.0% BCAA experimental groups, respectively. Body weight was measured on day 77, after which fish were fasted for 3 days and refed; the livers were then removed 3 or 9 h later for analysis of hepatic gene expression. Body weight significantly increased in the BCAA-supplemented groups. Hepatic expression of IGF1 and IGF2 significantly increased in the 2% BCAA group at 3 and 9 h after refeeding. In the 1% BCAA group, hepatic IGF1 expression tended to be higher at 9 h than in the control group after refeeding. Also, hepatic IGF2 significantly increased at only 9 h after refeeding in the 1% BCAA group. In conclusion, dietary supplementation with crystalline BCAAs increased growth and hepatic expression of IGF1 and IGF2. These results suggest that dietary crystalline BCAA supplementation would be a valuable addition to yellowtail aquaculture practices.

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein.

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet.

Effect of Roux-en-Y Gastric Bypass and Laparoscopic Adjustable Gastric Banding on Branched-Chain Amino Acid Metabolism

It has been hypothesized that a greater decline in circulating branched-chain amino acids (BCAAs) after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery than after calorie restriction alone has independent effects on glucose homeostasis, possibly by decreased signaling through the mammalian target of rapamycin (mTOR). We evaluated plasma BCAAs and their C3 and C5 acylcarnitine metabolites, muscle mTOR phosphorylation, and insulin sensitivity (insulin-stimulated glucose Rd) in obese subjects before and after ∼20% weight loss induced by RYGB (n = 10, BMI 45.6 ± 6.7 kg/m2) or laparoscopic adjustable gastric banding (LAGB) (n = 10, BMI 46.5 ± 8.8 kg/m2). Weight loss increased insulin-stimulated glucose Rd by ∼55%, decreased total plasma BCAA and C3 and C5 acylcarnitine concentrations by 20–35%, and did not alter mTOR phosphorylation; no differences were detected between surgical groups (all P values for interaction >0.05). Insulin-stimulated glucose Rd correlated negatively with plasma BCAAs and with C3 and C5 acylcarnitine concentrations (r values −0.56 to −0.75, P < 0.05). These data demonstrate that weight loss induced by either LAGB or RYGB causes the same decline in circulating BCAAs and their C3 and C5 acylcarnitine metabolites. Plasma BCAA concentration is negatively associated with skeletal muscle insulin sensitivity, but the mechanism(s) responsible for this relationship is not known.

Effects of eccentric exercise on branched‐chain amino acid profiles in rat serum and skeletal muscle

Supplementation of branched-chain amino acid (BCAA) is often used to attenuate exercise-induced skeletal muscle damage and promote adaptation, but no definitive conclusion on the benefits of BCAA on muscle recovery after injurious exercise can be drawn. Exploration of the systematic BCAA alteration in muscular injury-repair stage per se without any BCAA supplement should provide some useful information in favour of BCAA application in muscle regeneration after injury. One bout of 90-min downhill-running exercise was performed to cause rat skeletal muscle injury. After exercise, myofibrillar BCAA concentrations showed minor changes compared with exercise before, while serum concentrations of BCAA were lower after exercise. Especially, serum leucine, isoleucine and total BCAA concentrations 2 weeks post-run were significantly lower than normal values of exercise before (p = 0.008, p = 0.041, p = 0.015). The data demonstrate that a single eccentric exercise can significantly decrease the serum BCAA concentrations, which mean high utilization of BCAA for myogenesis after injurious exercise.

Is there In Vivo Evidence for Amino Acid Shuttles Carrying Ammonia from Neurons to Astrocytes?

The high in vivo flux of the glutamate/glutamine cycle puts a strong demand on the return of ammonia released by phosphate activated glutaminase from the neurons to the astrocytes in order to maintain nitrogen balance. In this paper we review several amino acid shuttles that have been proposed for balancing the nitrogen flows between neurons and astrocytes in the glutamate/glutamine cycle. All of these cycles depend on the directionality of glutamate dehydrogenase, catalyzing reductive glutamate synthesis (forward reaction) in the neuron in order to capture the ammonia released by phosphate activated glutaminase, while catalyzing oxidative deamination of glutamate (reverse reaction) in the astrocytes to release ammonia for glutamine synthesis. Reanalysis of results from in vivo experiments using (13)N and (15)N labeled ammonia and (15)N leucine in rats suggests that the maximum flux of the alanine/lactate or branched chain amino acid/branched chain amino acid transaminase shuttles between neurons and astrocytes are approximately 3-5 times lower than would be required to account for the ammonia transfer from neurons to astrocytes needed for glutamine synthesis (amide nitrogen) to sustain the glutamate/glutamine cycle. However, in the rat brain both the total ammonia fixation rate by glutamate dehydrogenase and the total branched chain amino acid transaminase activity are sufficient to support a branched chain amino acid/branched chain keto acid shuttle, as proposed by Hutson and coworkers, which would support the de novo synthesis of glutamine in the astrocyte to replace the ~20 % of neurotransmitter glutamate that is oxidized. A higher fraction of the nitrogen needs of total glutamate neurotransmitter cycling could be supported by hybrid cycles in which glutamate and tricarboxylic acid cycle intermediates act as a nitrogen shuttle. A limitation of all in vivo studies in animals conducted to date is that none have shown transfer of nitrogen for glutamine amide synthesis, either as free ammonia or via an amino acid from the neurons to the astrocytes. Future work will be needed, perhaps using methods for selectively labeling nitrogen in neurons, to conclusively establish the rate of amino acid nitrogen shuttles in vivo and their coupling to the glutamate/glutamine cycle.

Effect of pre-exercise single dose arginine ingestion on plasma amino acid profile during exhaustive exercise in elite male wrestlers

Aim: The aim of this study was to investigate the possible effects of pre-exercise single dose arginine ingestion on plasma amino acid profile during incremental exercise to exhaustion. Methods: Ten volunteer elite male wrestlers (age: 24.7±3.8) participated in this study. Testretest protocol was done on the same subjects. Exercise protocol started at 90 watts on bicycle ergometry and the load was increased 30 watts in every 3 min till the exhaustion. Arginine (1.5gr/10 kg body weight) or placebo were given to the subjects after 12 h fasting (during the night) and venous blood samples were collected 1 h after the supplementation (right before exercise protocol) and right after the exercise protocol for both test and retest. Plasma amino acid profiles were determined by HPLC. Results: Preand post-exercise arginine, ornithine and citrulline concentrations were significantly higher in arginine vs. placebo trial (p<0.05). Glutamine, tyrosine, methionine, phenylalanine, isoleucine and leucine concentrations increased following exercise only in arginine trial (p<0.05). Citrulline and tryptophan levels decreased while alanine levels increased after exercise in both trials (p<0.05). There was an increase following exhaustive exercise in total branched chain amino acid concentrations in arginine trial (p<0.05) whereas there is no significant change in placebo trial. Total amino acid concentrations were increased with exercise in both trials but post-exercise concentrations was higher in arginine trial compared to placebo trial (p<0.05). Conclusion: Results suggest that pre-exercise arginine supplementation can promote an amino acid profile that could be favorable for performance; however, further investigation is necessary to determine the effect of arginine supplementation on athletic performance.

Time-dependent changes in the plasma amino acid concentration in diabetes mellitus

We investigated longitudinal change in the amino acid (AA) profile in type 1 diabetes mellitus (DM) using AKITA mice, which develop DM as a result of insulin deficiency. The plasma concentrations of valine, leucine, isoleucine, as well as the total branched chain amino acids, alanine, citrulline and proline, were significantly higher in the diabetic mice. We show that the degree and timing of the changes were different among the plasma amino acid concentrations (pAAs) during the development of type 1 DM.

Effect of food form on postprandial plasma amino acid concentrations in older adults

To assess the effect of food form (FF) on postprandial (PP) plasma amino acid (AA) concentrations, ten older adults (five men and five women, age 72 (sem 2) years, BMI 26.0 (sem 0.9) kg/m2) consumed, on separate days, energy and macronutrient-matched test meal replacement products (MRP) (approximately 25 % of the subject's daily energy need; approximately 54 % carbohydrate, 21 % protein, 25 % fat) in beverage and solid form. Blood samples were taken during fasting and throughout the 4 h PP period; plasma AA concentrations were assessed using HPLC. Consumption of each MRP led to an increase in total AA, branched-chain AA (BCAA), essential AA (EAA), non-essential AA (NEAA) and leucine concentrations (4 h area under the curve, AUC) (time effect; P < 0.05). The beverage MRP resulted in a greater initial (i.e. 30 min) and sustained (4 h AUC) increase in total AA, BCAA, EAA, NEAA and leucine concentrations compared with the solid MRP (each effect of FF; P < 0.05). Although there was no effect of FF on PP insulin response, glucose concentration was greater 1 and 2 h after the solid MRP was consumed (FF × time interaction; P < 0.05). For all PP time points combined, total AA concentration was positively associated with plasma insulin (r 0.25) and glucose (r 0.24) concentrations for the solid MRP but not for the beverage MRP. In conclusion, older adults can achieve higher plasma AA concentrations when a protein-containing MRP is ingested in beverage form. The implications of the higher AA availability on anabolic processes warrant investigation.