Administration Of Amino Acids Research Articles

Multi-omics dataset of bovine mammary epithelial cells stimulated by ten different essential amino acids

Application of high-throughput sequencing and screening help to detect the transcriptional and metabolic discrepancies in organs provided with various levels of nutrients. The influences of individual essential amino acid (EAA) administration on transcriptomic and metabolomic profilings of bovine mammary epithelial cells (BMECs) were systematically investigated. A RNA sequencing and liquid chromatography-tandem mass spectrometry generated a comprehensive comparison of transcriptomics, non-targeted metabolomics and targeted amino acids profilings of BMECs with individual EAA stimulation by turn. The sequencing data and raw LC-MS/MS data of samples were presented in the databases of Gene Expression Omnibus, MetaboLights and Figshare for efficient reuse, including exploring the divergences in metabolisms between different EAAs and screening valuable genes and metabolites regulating casein synthesis.

Short-term parenteral infusions with high-osmolality amino acid solutions can be safely administered through peripheral catheters in dogs treated for hypoaminoacidemia-related conditions.

To compare complications between central and peripheral administration of high-osmolarity (approx 700 to 1,000 mOsm/L) amino acid (± lipid) infusions. 18 client-owned dogs diagnosed with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome or superficial necrolytic dermatitis receiving parenteral amino acid ± lipid infusions. In this retrospective case series, medical records were reviewed for administration route (central vs peripheral), catheter details and infusion characteristics (product osmolarity, concurrent lipid administration, infusion volume, duration, and rate), and complications for each infusion. 18 dogs received 277 infusions (median, 8.5; range, 1 to 84). Effective infusion osmolarities were 683 mOsm/L in 22% of infusions, 791 mOsm/L in 8%, 802 mOsm/L in 2%, 837 mOsm/L in 45%, and 998 mOsm/L in 23% (65% peripheral, 35% central). Most (n = 230 [83%]) infusions were given peripherally. The osmolarities of solutions administered by each route (P = .53), the infusion rate indexed to body weight (P = .17), or the lipid infusion rates indexed to body weight (P = .89) did not differ. One dog suffered 2 complications in 63 infusions-1 mild, 1 severe-both occurring with peripheral infusions. Thus, the overall complication rate was 2 of 277 (0.9%) infusions. Short-term peripherally administered amino acid ± lipid infusions < 1,000 mOsm/L confer little risk compared to centrally administered infusions. Additional studies are needed to determine the safety of infusions with longer durations. Due to the relative ease of peripheral catheterization, clinicians should consider this route for medically managing aminoaciduric canine hypoaminoacidemic hepatopathy syndrome and superficial necrolytic dermatitis in dogs.

Administration of Free Amino Acids Improves Exogenous Amino Acid Availability when Compared with Intact Protein in Critically Ill Patients: A Randomized Controlled Study

BackgroundProtein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may improve postprandial amino acid availability. ObjectiveOur objective was to quantify the uptake of diet-derived phenylalanine after the enteral administration of intact protein compared with an equivalent amount of free amino acids in critically ill patients. MethodsSixteen patients who were mechanically ventilated in intensive care unit (ICU) at risk of malabsorption received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine after an overnight fast. Patients were randomly allocated to receive 20 g intrinsically L-[1-13C]-phenylalanine-labeled milk protein or an equivalent amount of amino acids labeled with free L-[1-13C]-phenylalanine via a nasogastric tube over a 2-h period. Protein digestion and amino acid absorption kinetics and whole-body protein net balance were assessed throughout a 6-h period. ResultsAfter enteral nutrient infusion, both plasma phenylalanine and leucine concentrations increased (P-time < 0.001), with a more rapid and greater rise after free amino acid compared with intact protein administration (P-time × treatment = 0.003). Diet-derived phenylalanine released into the circulation was 25% greater after free amino acids compared with intact protein administration [68.7% (confidence interval {CI}: 62.3, 75.1%) compared with 43.8% (CI: 32.4, 55.2%), respectively; P < 0.001]. Whole-body protein net balance became positive after nutrient administration (P-time < 0.001) and tended to be more positive after free amino acid in provision (P-time × treatment = 0.07). ConclusionsThe administration of free amino acids as opposed to intact protein further increases postprandial plasma amino acid availability in critically ill patients, allowing more diet-derived phenylalanine to become available to peripheral tissues.This trial was registered at clinicaltrials.gov as NCT04791774.

Use of non-canonical amino acids in genetic code expansion-based therapeutics: Effects on mouse gut microbiota.

Vaccines and cell therapeutics based on genetic code expansion are emerging. A crucial step in these therapeutic technologies is the oral administration of non-canonical amino acids (ncAAs) to control pathogen growth and therapeutic protein levels invivo. Investigating the toxicity effects of ncAAs can help identify more suitable candidates for developing genetic code expansion-based vaccines and cell therapeutics. In this study, we determined the effects of three ncAAs, namely, 4-acetyl-phenylalanine (pAcF), 4-iodo-phenylalanine (pIoF), and 4-methoxy-phenylalanine (pMeoF), commonly used in genetic code expansion-based vaccines and cell therapeutics, on the main organs, serum biochemical parameters, and gut microbiota in mice. We observed that pIoF and pMeoF significantly altered serum biochemical parameters to some extent. Moreover, the alterations in the mouse gut microbial composition were considerably greater after the oral administration of pIoF and pMeoF than after that of pAcF, compared with that in the control mice. These findings suggest that pAcF is more suitable than pIoF and pMeoF for application in genetic code expansion-based vaccines and cell therapeutics as it disturbs the physiological and gut microecological balance in mice to a lesser extent.

Perioperative Intravenous Amino Acid Infusion in Major Urologic Surgery.

Post-operative acute kidney injury (PO-AKI) is a serious complication that may occur after major abdominal surgery. The administration of intravenous perioperative amino acids (AAs) has been proven to increase kidney function and has some beneficial effects to prevent PO-AKI. The aim of this study was to establish if the perioperative infusion of AAs may reduce the incidence of PO-AKI in patients undergoing major urological minimally invasive surgery. From a total of 331 patients, the first 169 received perioperative crystalloid fluids and the following 162 received perioperative AA infusions. PO-AKIs were much higher in the crystalloid group compared to the AA group (34 vs. 17, p = 0.022) due to a lower incidence of KDIGO I and II in the AA group (14 vs. 30 p = 0.016). The AA group patients who developed a PO-AKI presented more risk factors compared to those who did not (2 (2-4) vs. 1 (1-2), p = 0.031) with a cut-off of 3 risk factors in the ROC curve (p = 0.007, sensitivity 47%, specificity 83%). The hospital length of stay was higher in the crystalloid group (p < 0.05) with a consequent saving in hospital costs. Perioperative AA infusion may help reduce the incidence of PO-AKI after major urological minimally invasive surgery.

Effects of branched-chain amino acids supplementation on patients undergoing hepatic intervention: a meta-analysis of randomised controlled trials.

The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention.

Short-term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates.

The decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short-term disuse, when atrophy rates are the highest. We sought to determine whether 2days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions. Twenty-three healthy, male participants (age: 22±1year; height: 179±1cm; body mass: 73.4±1.5kg; body mass index 22.8±0.5kg·m-2 ) took part in this randomized, controlled study. After 48h of unilateral knee immobilization, primed continuous intravenous l-[15 N]-phenylalanine and l-[ring-2 H5 ]-phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5mg·kg body mass-1 ·h-1 amino acid infusion; FED). Bilateral m. vastus lateralis biopsies from the control (CON) and immobilized (IMM) legs, and arterialized-venous blood samples, were collected throughout. Amino acid infusion rapidly increased plasma phenylalanine (59±9%), leucine (76±5%), isoleucine (109±7%) and valine (42±4%) concentrations in FED only (all P<0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8±2.2mU·L-1 at 15min in FED only (P<0.001) and were 60% greater in FED than FAST (P<0.01). Immobilization did not influence FBR in either FAST (CON: 0.150±0.018; IMM: 0.143±0.017%·h-1 ) or FED (CON: 0.134±0.012; IMM: 0.160±0.018%·h-1 ; all effects P>0.05). However, immobilization decreased FSR (P<0.05) in both FAST (0.071±0.004 vs. 0.086±0.007%·h-1 ; IMM vs CON, respectively) and FED (0.066±0.016 vs. 0.119±0.016%·h-1 ; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (P<0.05) and to a greater extent in FED (CON: -0.012±0.025; IMM: -0.095±0.023%·h-1 ; P<0.05) than FAST (CON: -0.064±0.020; IMM: -0.072±0.017%·h-1 ). We conclude that merely 2days of leg immobilization does not modulate postabsorptive and simulated postprandial muscle protein breakdown rates. Instead, under these conditions the muscle negative muscle protein balance associated with brief periods of experimental disuse is driven near exclusively by reduced basal muscle protein synthesis rates and anabolic resistance to amino acid administration.

Estimates of the Effect of Feeding on Whole-Body Protein Degradation in Women Vary with the Amino Acid Used as Tracer

We measured how feeding status affects the kinetics of multiple indispensable amino acids in four adult female subjects studied both in fed and fasted state. The subjects ingested one dose of uniformly 13C-labeled algae (Spirulina platensis). The isotopic enrichments (measured with negative chemical ionization gas chromatography-mass spectrometry) of the branched chain amino acids, phenylalanine, lysine and threonine were followed for 24 h in both the plasma and in VLDL-apolipoprotein B-100 (apoB-100). Fasting lowered body protein degradation when measured with the branched chain amino acids, increased it when measured with phenylalanine and had no statistically significant effect when determined from the kinetics of lysine and threonine. These apparent differences challenge the adequacy of current models of whole-body protein turnover. The ratio of the peak labeling of amino acids in plasma and apoB-100 was used as an estimate of the isotopic dilution in the hepatic pool. In contrast to our earlier observations during intravenous tracer amino acid administration, in the present study fasting lowered the ratio of the peak isotopic enrichments of apoB-100 and plasma amino acids. This supports our contention that feeding increases the use of hepatic portal amino acids for hepatic secretory protein synthesis.

Postprandial secretion of follistatin after gastric bypass surgery and sleeve gastrectomy

Follistatin is secreted from the liver and may regulate muscle growth and insulin sensitivity. Protein intake stimulates follistatin secretion, which may be mediated by increased glucagon in the context of low insulin concentrations. We investigated circulating follistatin after mixed-meals in two cohorts of patients who were part of previously published studies and had undergone bariatric surgery with either simultaneous assessment of amino acid absorption or administration of the GLP-1 receptor antagonist exendin-(9−39), which increased glucagon concentrations and impaired insulin secretion. Study 1 comprised obese matched subjects with previous Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery and unoperated controls who underwent 6-hour mixed-meal tests with intravenous and oral tracers including intrinsically labelled caseinate in the meal. Study 2 comprised obese subjects with previous RYGB who underwent two 5-hour mixed-meal tests with concomitant exendin-(9−39) or saline infusion. In study 1, the secretion of follistatin as well as the amino acid absorption was accelerated after RYGB compared with SG and controls, but the glucagon-to-C-peptide ratios did not differ between the groups. In study 2, exendin-(9−39) administration increased postprandial glucagon concentrations and lowered insulin secretion, whereas the concentration of follistatin was unchanged. In conclusion, postprandial follistatin secretion is accelerated in patients after RYGB which might be explained by an accelerated protein absorption rate rather than the glucagon-to-insulin ratio.

Effects of amino acids and albumin administration on albumin metabolism in surgically stressed rats: A basic nutritional study.

Nutrition therapy and administration of albumin preparations are common in postsurgical patients. However, the effects of these interventions on albumin metabolism are unclear. We elucidated the effect of postoperative albumin and/or parenteral nutrition administration on it. Sprague-Dawley rats underwent surgery involving intestinal rubbing followed by intestinal exposure. Subsequently, they were administered experimental solutions for 48 h, their blood samples were collected at 24 and 48 h, and livers were excised at 48 h. Based on experimental solutions, rats were divided into five groups: non-surgical (Non-surg); glucose and electrolyte solution (GE); amino acid, glucose, and electrolyte solution (AGE); GE + rat serum albumin (Alb) (GE + Alb); and AGE + Alb. Their plasma albumin concentrations; albumin fractional synthesis rate (ALB FSR); mercaptoalbumin/total albumin ratio (MA ratio); and messenger RNA (mRNA) expressions of albumin and hepatocyte nuclear factor-1 (HNF-1) in the liver were measured. The GE and AGE groups showed significant decline in albumin concentrations. ALB FSR was significantly enhanced in the AGE group compared with the GE group. The mRNA expression of albumin was similar to ALB FSR in all groups and that of HNF-1 was significantly decreased in the GE + Alb and AGE + Alb groups compared with the Non-surg group. The MA ratio in the AGE group was similar to the Non-surg group. The administration of amino acids comprising parenteral nutrition after surgery augmented ALB FSR and maintained the MA ratio only without simultaneous albumin administration.

Preoperative administration of branched-chain amino acids reduces postoperative insulin resistance in rats by reducing liver gluconeogenesis

BackgroundPostoperative insulin resistance (PIR) represents an important characteristic of metabolic response following surgical injury. Clinical outcomes are negatively correlated to postoperative insulin resistance and hyperglycemia, indicating a novel treatment for reducing postoperative insulin resistance is urgently needed. The current work aimed to assess the protective effects of branched-chain amino acids (BCAA) on glucose metabolism disorders induced surgically in a rat model, and to explore the underpinning mechanism.Methods and resultsRats were randomly assigned to 2 groups, including the control and BCAA groups. Rats were given a compulsory oral 3 mL load by gavage two hours before surgery. The results showed that BCAA remarkably reduced glycemia by suppressing liver gluconeogenesis via reduction of cAMP-response element-binding protein-regulated transcription coactivator 2 (CRTC2) and glucose-6-phosphatase (G6PC) gene and protein expression levels (all Ps < 0.05).ConclusionsThis study revealed that BCAA lower blood glucose levels by reducing liver gluconeogenesis without significant elevation of plasma insulin levels. We anticipate that preoperative BCAA supplementation may be a means for preventing postoperative insulin resistance.

Oral Administration of Branched-Chain Amino Acids Attenuates Atherosclerosis by Inhibiting the Inflammatory Response and Regulating the Gut Microbiota in ApoE-Deficient Mice

Atherosclerosis (AS) is a chronic inflammatory disease that serves as a common pathogenic underpinning for various cardiovascular diseases. Although high circulating branched-chain amino acid (BCAA) levels may represent a risk factor for AS, it is unclear whether dietary BCAA supplementation causes elevated levels of circulating BCAAs and hence influences AS, and the related mechanisms are not well understood. Here, ApoE-deficient mice (ApoE-/-) were fed a diet supplemented with or without BCAAs to investigate the effects of BCAAs on AS and determine potential related mechanisms. In this study, compared with the high-fat diet (HFD), high-fat diet supplemented with BCAAs (HFB) reduced the atherosclerotic lesion area and caused a significant decrease in serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. BCAA supplementation suppressed the systemic inflammatory response by reducing macrophage infiltration; lowering serum levels of inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6); and suppressing inflammatory related signaling pathways. Furthermore, BCAA supplementation altered the gut bacterial beta diversity and composition, especially reducing harmful bacteria and increasing probiotic bacteria, along with increasing bile acid (BA) excretion. In addition, the levels of total BAs, primary BAs, 12α-hydroxylated bile acids (12α-OH BAs) and non-12α-hydroxylated bile acids (non-12α-OH BAs) in cecal and colonic contents were increased in the HFB group of mice compared with the HFD group. Overall, these data indicate that dietary BCAA supplementation can attenuate atherosclerosis induced by HFD in ApoE-/- mice through improved dyslipidemia and inflammation, mechanisms involving the intestinal microbiota, and promotion of BA excretion.

Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmitter hydrogen sulfide (H2S). Here we show that the C. elegans DMD model displays reduced levels of H2S and expression of genes required for sulfur metabolism. These reductions can be offset by increasing bioavailability of sulfur containing amino acids (L-methionine, L-homocysteine, L-cysteine, L-glutathione, and L-taurine), augmenting healthspan primarily via improved calcium regulation, mitochondrial structure and delayed muscle cell death. Additionally, we show distinct differences in preservation mechanisms between sulfur amino acid vs H2S administration, despite similarities in required health-preserving pathways. Our results suggest that the H2S deficit in DMD is likely caused by altered sulfur metabolism and that modulation of this pathway may improve DMD muscle health via multiple evolutionarily conserved mechanisms.

PMON68 Effect of an Amino-Acid Based Blend on Human Growth Hormone (hGH) and Fibromyalgia (FM) Symptoms

Abstract Fibromyalgia is a chronic pain sensitivity disorder that affects approximately 3-8% of the general population with symptoms that include fatigue and widespread musculoskeletal pain. Psychological and physical stressors are frequent drivers of fibromyalgia, and additional lockdown-associated stressors may worsen symptoms. Reduced production of human growth hormone (hGH) is evident in approximately 30% of individuals with fibromyalgia, which is hypothesized to contribute to common fibromyalgia symptoms. An orally administered amino acid supplement has been previously shown to improve endogenous hGH status in adults. We investigated if daily administration of the supplement would increase levels of endogenous insulin-like growth factor 1 (IGF-1), a surrogate marker of the body's hGH levels, and improve symptoms related to low-normal hGH production in a cohort of 84 individuals being treated for fibromyalgia. This is the full-cohort analysis of an open-label, single-arm study that investigated the effects of 24 weeks of daily oral administration of the supplement in individuals with low-normal hGH production. The primary endpoint was the change from baseline to endpoint (Week 24) in serum IGF-1. Additional endpoints included the change in body weight, clinical symptoms (assessed with the Revised Fibromyalgia Impact Questionnaire [FIQR], range 0-100, and Perceived Stress Scale [PSS], range 0-40), fasting cardiometabolic markers, tolerability, and safety. Participants continued to receive standard care. The study enrolled 84 fibromyalgia patients with low-normal age-adjusted IGF-1 serum levels. High mean±SD baseline FIQR and PSS scores of 76±16 and 32±5, respectively, indicated poor to moderate symptom management with standard care. All individuals completed 24 weeks of treatment. Serum IGF-1 levels increased with a Week 24 mean±SE change of 28.4±3.0 ng/mL (paired t-test p&amp;lt;0.001). Body weight was reduced with a Week 24 mean±SE change of -5.5±0.3 kg (p&amp;lt;0.001). The change from baseline in FIQR and PSS scores were -29.1±1.1 and -20.0±0.8, respectively (both p&amp;lt;0.001), indicating a substantial improvement. Statistically significant improvements from baseline were also observed for systolic and diastolic blood pressure, HbA1c, LDL and HDL cholesterol, and triglycerides (all p&amp;lt;0.001). The supplement was well tolerated; no adverse events were reported. Sustained augmentation of IGF-1 with the supplement may represent a unique method of improving clinical symptoms of fibromyalgia in individuals with low-normal hGH production. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Branched-chain amino acids (BCAA) administration increases autophagy and the autophagic pathway in brain tissue of rats submitted to a Maple Syrup Urine Disease (MSUD) protocol.

Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism (EIM) biochemically characterized by the tissue accumulation of branched-chain amino acids (BCAA) and their branched-chain alpha-keto acids. The mechanisms by which BCAA and their branched-chain alpha-keto acids lead to the neurological damage observed in MSUD are poorly understood. Mounting evidence has demonstrated that BCAA induce the overproduction of reactive oxygen species, which may modulate several important signaling pathways necessary for cellular homeostasis maintenance, such as autophagy. Taking this into account, we evaluated the effects of BCAA on the autophagic pathway in brain structures of rats submitted to the administration of these amino acids (animal model of MSUD). Our findings showed that BCAA significantly increased the levels of Beclin-1, ATG7, and ATG5 in the cerebral cortex of rats. In addition, BCAA augmented ATG12 levels in the striatum and ATG5 and LC3 I-II in the hippocampus. Therefore, our work demonstrates that the administration of BCAA increases autophagy and autophagic cell death, possibly mediated by the elevated levels of reactive species generated by BCAA.

Design and Modelling a Graduated Dispenser for Metabolic Diseases—Phenylketonuria

In metabolic diseases such as phenylketonuria (a rare disease), a very important way to keep the patient healthy is the administration of amino acid substitutes. This dispenser was designed because in other places (except home) for patients, it is very difficult to take the substitute powder due to the custom weight, which depends on the body weight. We designed and made on a 3D printer a graduated dosing device (12 g) which can be used very easily and has all the elements to be transported. In this way, the necessary dose of amino acid substitutes can be administered to patients with phenylketonuria, including infants aged 6 months–1 year, at the kindergarten or any other places with the absence of a food scale. This dispenser is very easy to carry and very useful to patients.

Carbamylation of Integrin α IIb β 3: The Mechanistic Link to Platelet Dysfunction in ESKD.

Bleeding diatheses, common among patients with ESKD, can lead to serious complications, particularly during invasive procedures. Chronic urea overload significantly increases cyanate concentrations in patients with ESKD, leading to carbamylation, an irreversible modification of proteins and peptides. To investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin α IIb β 3 (a receptor required for platelet aggregation). Flow cytometry was used to study activation of isolated platelets and platelet-rich plasma. In a transient transfection system, we tested activity and fibrinogen binding of different mutated forms of the receptor. We assessed platelet adhesion and aggregation in microplate assays. Carbamylation inhibited platelet activation, adhesion, and aggregation. Patients on hemodialysis exhibited significantly reduced activation of α IIb β 3 compared with healthy controls. We found significant carbamylation of both subunits of α IIb β 3 on platelets from patients receiving hemodialysis versus only minor modification in controls. In the transient transfection system, modification of lysine 185 in the β 3 subunit was associated with loss of receptor activity and fibrinogen binding. Supplementation of free amino acids, which was shown to protect plasma proteins from carbamylation-induced damage in patients on hemodialysis, prevented loss of α IIb β 3 activity in vitro. Carbamylation of α IIb β 3-specifically modification of the K185 residue-might represent a mechanistic link between uremia and dysfunctional primary hemostasis in patients on hemodialysis. The observation that free amino acids prevented the carbamylation-induced loss of α IIb β 3 activity suggests amino acid administration during dialysis may help to normalize platelet function.

Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms.

Branched-chain amino acids (BCAAs), essential amino acids for the human body, are mainly obtained from food. High levels of BCAAs in circulation are considered as potential markers of metabolic-associated fatty liver disease (MAFLD) in humans. However, there are conflicting reports about the effects of supplement of BCAAs on MAFLD, and research on BCAAs and gut microbiota is not comprehensive. Here, C57BL/6J mice were fed with a high-fat diet with or without BCAAs to elucidate the effects of BCAAs on the gut microbiota and metabolic functions in a mouse model of MAFLD. Compared to high-fat diet (HFD) feeding, BCAA supplementation significantly reduced the mouse body weight, ratio of liver/body weight, hepatic lipid accumulation, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT), and the expressions of the lipogenesis-related enzymes Fas, Acc, and Scd-1 and increased expressions of the lipolysis-related enzymes Cpt1A and Atgl in the liver. BCAAs supplementation also counteracted HFD-induced elevations in serum BCAAs levels by stimulating the enzymatic activity of BCKDH. Furthermore, BCAAs supplementation markedly improved the gut bacterial diversity and altered the gut microbiota composition and abundances, especially those of genera, in association with MAFLD and BCAAs metabolism. These data suggest that BCAA treatment improves HFD-induced MAFLD through mechanisms involving intestinal microbes.

Administration of Branched-Chain Amino Acids in the Pre- or Post-Hatch Period Improves the Fiber Characteristics of Pectoralis major Muscle in Turkey Poults Subjected to Early or Delayed Feeding

Poultry meat quality is controlled by muscle fiber properties associated with body weight gain in the immediate pre- or post-hatch period. This study aimed to determine the effect of administration of branched-chain amino acids blend (BCAAb, 3 L-leucine:1 L-isoleucine:2 L-valine) in the pre- or post-hatch period on the growth performance and fiber characteristics of the Pectoralis major (PM) muscle in turkey poults subjected to early or delayed feeding. Newly hatched poults from eggs injected in ovo with BCAAb or received no injection were used in a 21-d study. Poults (n=192) produced without injection of BCAAb received a starter diet supplemented (BCAA) or not (C) with the BCAAb (2 g/kg) immediately or with a delay of 48 h (48BCAA and 48C) after hatching. Poults (n=36) produced with (IOBCAA) in ovo injection of BCAAb (2 mg /ml) received the diet and water immediately. The BCAA and IOBCAA poults had higher body weight than those of the C, 48C, and 48BCAA birds. The body weight of the C poults was higher than those of the 48C and 48BCAA birds. The BCAA poults had higher PM muscle weight than those of the C and 48C poults, while that of the IOBCAA poults was higher than that of the 48C poults. The IOBCAA treatment increased the protein content of the PM muscle meat, compared with the C and 48C treatments. The 48C treatment increased the type IIB fiber area and the type I and type IIA fiber percentages but decreased the type IIB fiber, compared with other treatments. The numbers of type IIB and total fibers in the IOBCAA poults were higher than those of the 48C birds. In conclusion, administering BCAAb in ovo or in a starter diet enhanced early growth performance and improved the fiber characteristics of the PM muscle in turkey poults.

Early high dose versus low dose parenteral amino acids administration in the preterm infants: A meta-analysis

Objective: Preterm infants may face difficulty on getting the nutrition required for growth due to incompetence of sucking and immaturity of the gastrointestinal. Preterm infants require higher amounts of amino acids and protein to support the growth of lean body mass and tissue. Administrating amino acid supplementation during the first hour of life is the key to preventing early neonatal malnutrition and can be beneficial in the growth of the neonates. Objectives: Aim of this study is to determine the effects of early high dose parenteral amino acids administration versus low dose in preterm infants from all collected studies. Methods: This is a meta-analysis study that studies were collected MedLine, PubMed, and Cochrane Central Register of Controlled Trials comparing early high dose parenteral amino acids versus low dose. High-quality studies, as assessed by Jadad Criteria, were used to evaluate outcomes such as anthropometric data, length of hospital stays, and morbidities. Results: A total of 9 Randomized controlled trials (RCTs) with total of 960 participants were included in the analysis. Analysis of these studies showed a statistically significant reduction in the time to regain birth weight in the group of early high-dose amino acids administration in the preterm infants. Reductions were 0.79 day (MD 0.79 day, 95% CI 0.06 to 1.52 day; participants = 655; studies = 6; I2 = 0%) (P= 0.03). It also showed a statistically significant reduction in the length of stay with a reduction of 2.09 days in the early high-dose parenteral amino acids groups (MD 2.09 days, 95% CI 1.01 to 3.17 day; participants = 500; studies = 5; I2 = 0%) (P= 0.0002). No significant difference in morbidity of each group was found. Conclusion: Administration of early high-dose amino acids reduced the time to regain birth weight and the length of hospitalization in preterm infants. The analysis did not show any significant increase in the risk of morbidity.