Plasma Amino Acid Concentrations Research Articles

L-Leucine supplementation reduces growth performance accompanied by changed profiles of plasma amino acids and expression of jejunal amino acid transporters in breast-fed intra-uterine growth-retarded piglets.

Previously, we provided an evidence that l-Leucine supplementation facilitates growth performance in suckling piglets with normal birth weight. However, it remains hitherto obscure weather breast-fed piglets displaying intra-uterine growth restriction (IUGR) show a similar effect in response to l-Leucine provision. In this study, 7-d-old sow-reared IUGR piglets were orally administrated with l-Leucine (0, 0·7, 1·4 or 2·1 g/kg BW) twice daily for 2 weeks. Increasing leucine levels hampered the growth performance of suckling IUGR piglets. The average daily gain of IUGR piglets was significantly reduced in 1·4 g/kg BW and 2·1 g/kg BW l-Leucine supplementation groups (P < 0·05). Except for ornithine and glutamine, the plasma concentrations of other amino acids were abated as l-Leucine levels increased (P < 0·05). Leucine supplementation led to reduction in the levels of urea, blood ammonia, blood glucose, TAG and total cholesterol, as well as an elevation in the level of LDL-cholesterol in suckling IUGR piglets (P < 0·05). In addition, 1·4 g/kg BW of l-Leucine enhanced the mRNA expression of ATB0,+, whereas decreased the mRNA abundances of CAT1, y + LAT1, ASCT2 and b0,+AT in the jejunum (P < 0·05). Concomitantly, the jejunum of IUGR piglets in l-Leucine group contains more ATB0,+ and less SNAT2 protein than in the control (P < 0·05). Collectively, l-Leucine supplementation impairs growth performance in breast-fed IUGR piglets, which may be associated with depressed nutritional conditions and alterations in the uptake of amino acids and the expression of amino acid transporters in the small intestine.

Four weeks treatment with the GLP-1 receptor analogue liraglutide lowers liver fat and concomitantly circulating glucagon in individuals with overweight.

We investigated the effect of pharmacologically induced weight loss on markers of glucagon resistance in individuals with overweight during treatment with the glucagon-like peptide-1 receptor agonist liraglutide. We performed an open-label study in 14 men with overweight (age 38 ± 11 years, BMI 32 ± 4 kg/m2) without simultaneously diabetes. Subjects were treated with liraglutide, initiated and titrated with 0.6 mg/day/week to reach the final dose of 3.0 mg/day. Subjects were examined at baseline, during titration (Week 4), after 2 weeks of steady state (Week 6) of final dosing of liraglutide and 3 weeks after discontinuation of liraglutide (follow-up). Study participants lost 3.3 ± 1.9 kg (3%) total body weight during the first 4 weeks of treatment with liraglutide. Simultaneously, liver fat content decreased from 12.4 ± 11.6% to 10.2 ± 11.1%, p = 0.025, whereas fat content in the spleen and subcutaneous tissue was unaltered. Markers of glucagon resistance, including plasma glucagon and the glucagon-alanine-index, also decreased significantly during treatment, but total and individual plasma amino acid concentrations did not. Insulin resistance (HOMA-IR) was unchanged during treatment, whereas insulin clearance increased. Treatment with the GLP-1 receptor analogue liraglutide decreased liver fat content, and simultaneously attenuated glucagon concentrations and the glucagon-alanine index in individuals with overweight without diabetes.

Dietary choline supplementation increases the plasma concentration of several amino acids during atherosclerosis development

Background and Aims : Increased dietary intake of choline worsens the development of atherosclerosis in ApoE-KO mice. Gut microbial metabolism of choline results in the production of trimethylamine, which, upon intestinal absorption is converted into the pro-atherogenic molecule trimethylamine-N-oxide (TMAO) in the liver. In this study we investigated if additional endogenous plasma metabolites were modulated by increased choline intake.

Differential effect of two dietary protein sources on time course response of muscle anabolic signaling pathways in normal and insulin dysregulated horses.

The objective of the study was to characterize the temporal changes of phosphorylation patterns of mTOR signaling proteins in response to two dietary protein sources in insulin dysregulated (ID, n = 8) and non-ID (n = 8) horses. Horses were individually housed and fed timothy grass hay and 2 daily concentrate meals so that protein was the first limiting nutrient and the total diet provided 120% of daily DE requirements for maintenance. On sample days, horses randomly received 0.25 g CP/kg BW of a pelleted alfalfa (AP) or commercial protein supplement (PS). Blood samples were collected before and 30, 60, 90, 120, 150, 180, 210, 240, 300, 360, 420, and 480 min post feeding and analyzed for plasma glucose, insulin and amino acid (AA) concentrations. Gluteus Medius muscle samples were obtained before and 90, 180, and 300 min after feeding and analyzed for relative abundance of phosphorylated mTOR pathway components using western immunoblot analysis. There was no effect of protein source on postprandial glucose and insulin responses (P ≥ 0.14) but consumption of PS elicited a 2 times larger AUC for essential AA (EAA), greater peak concentrations of EAA and a shorter time to reach peak EAA concentrations compared to AP. Abundance of phosphorylated mTOR (P = 0.08) and rpS6 (P = 0.10) tended to be ~1.5-fold greater after consumption of PS at 90 min compared to AP. Dephosphorylation patterns differed between protein sources and was slower for AP compared to PS. ID horses had a 2 times greater (P = 0.009) AUC and 3 times higher postprandial peak concentrations (P < 0.0001) for insulin compared to non-ID horses after consumption of both treatment pellets, but EAA responses were similar between groups (P = 0.53). Insulin status did not affect rpS6 or mTOR phosphorylation after consumption of either protein source (P ≥ 0.35), but phosphorylated rpS6 abundance was twice as high in ID compared to non-ID horses (P = 0.007). These results suggest that the consumption of higher quality protein sources may result in greater postprandial activation of the mTOR pathway compared to equal amounts of a forage-based protein source. Moreover, ID does not impair postprandial activation of mTOR and rpS6 proteins in horses following a protein-rich meal.

O25 Milk and plasma amino acid concentration response to abomasal or intra-venous amino acid infusion in dairy cows

O25 Milk and plasma amino acid concentration response to abomasal or intra-venous amino acid infusion in dairy cows

Alteration of Plasma Amino Acid Concentrations in Iranian Children with COVID-19.

COVID-19 is an acute viral disease that has so far infected more than 200 million and killed more than four million worldwide. It affects the immune system and other organs. Here, we investigated the level of free plasma amino acids in COVID-19 patients and compared them with non-COVID-19 subjects. We also compared amino acids levels in critically ill patients admitted to the intensive care unit (ICU) with non-ICU patients and expired and recovered patients. Twenty-six COVID-19 patients and 32 non-COVID-19 subjects were included in the study. The mean of glutamic acid, serine, glycine, threonine, phenylalanine, leucine, lysine, alanine, arginine, aspartic acid, and ornithine was significantly higher in cases than controls. In addition, the mean of glutamine was significantly lower in patients than controls (443.89 ± 254.31 vs. 651.73 ± 107.38, PV < 0.001). Low level of glutamine and isoleucine was seen in the majority of ICU and expired patients, respectively. Logistic regression analysis showed low level of isoleucine as a predictor variable in mortality (P = 0.02, EXP (B) = 16.5, and CI 95% = (1.48, −183.07)). There was a positive and significant relationship between some amino acids levels, serum liver enzymes, and sodium concentrations. There was also a significant but negative correlation between histidine levels, ESR, and ferritin. Phenylalanine had a highly positive relationship with serum procalcitonin in patients (R2 = 0.534, PV = 0.015). Our studies have shown the alteration of plasma amino acids concentration in COVID-19 patients. These changes are more evident in critically ill and at-risk patients.

Correlation of Salivary Occult Blood with the Plasma Concentration of Branched-Chain Amino Acids: A Cross-Sectional Study.

Background: Plasma branched-chain amino acids (BCAA) levels are predictors of glycometabolic disorders, leading to diabetes. Microbes, including periodontal pathogens, are thought to be associated with elevated plasma BCAA levels. This study aimed to evaluate the relationship between salivary occult blood (SOB) and plasma BCAA levels in middle-aged Japanese individuals. Methods: Sixty-four Japanese individuals aged ≥ 40 years were recruited for this study, which was conducted in Fukuoka Prefecture, Japan, from August to December 2021. Individuals diagnosed with and/or treated for diabetes were excluded from the study. The body mass index (BMI); plasma concentrations of total, high-density, and low-density lipoprotein cholesterol; triglyceride, glucose, and BCAA; and glycosylated hemoglobin ratio were measured. A basic periodontal examination was performed after the SOB test. Results: The median age of participants (men—20; women—44) was 55 (range, 41–78) years. The plasma BCAA concentration in the SOB-positive group (477 [400–658] μmol/L) was higher than that in the SOB-negative group (432 [307–665] μmol/L). Linear regression analysis revealed that SOB remained independently associated with the plasma BCAA level with statistical significance (β = 0.17, p = 0.02) after adjusting for sex, age, and BMI. Conclusions: SOB was positively correlated with plasma BCAA levels in middle-aged Japanese individuals. Thus, SOB may be a predictor of elevated plasma BCAA levels.

Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients.

Patients dependent on chronic hemodialysis treatment are prone to malnutrition, at least in part due to insufficient nutrient intake, metabolic derangements, and chronic inflammation. Losses of amino acids during hemodialysis may be an important additional contributor. In this study, we assessed changes in plasma amino acid concentrations during hemodialysis, quantified intradialytic amino acid losses, and investigated whether plasma amino acid concentrations and amino acid losses by hemodialysis and urinary excretion are associated with fatigue. The study included a total of 59 hemodialysis patients (65 ± 15 years, 63% male) and 33 healthy kidney donors as controls (54 ± 10 years, 45% male). Total plasma essential amino acid concentration before hemodialysis was lower in hemodialysis patients compared with controls (p = 0.006), while total non-essential amino acid concentration did not differ. Daily amino acid losses were 4.0 ± 1.3 g/24 h for hemodialysis patients and 0.6 ± 0.3 g/24 h for controls. Expressed as proportion of protein intake, daily amino acid losses of hemodialysis patients were 6.7 ± 2.4% of the total protein intake, compared to 0.7 ± 0.3% for controls (p < 0.001). Multivariable regression analyses demonstrated that hemodialysis efficacy (Kt/V) was the primary determinant of amino acid losses (Std. β = 0.51; p < 0.001). In logistic regression analyses, higher plasma proline concentrations were associated with higher odds of severe fatigue (OR (95% CI) per SD increment: 3.0 (1.3; 9.3); p = 0.03), while higher taurine concentrations were associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.3 (0.1; 0.7); p = 0.01). Similarly, higher daily taurine losses were also associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.64 (0.42; 0.93); p = 0.03). Lastly, a higher protein intake was associated with lower odds of severe fatigue (OR (95% CI) per SD increment: 0.2 (0.04; 0.5); p = 0.007). Future studies are warranted to investigate the mechanisms underlying these associations and investigate the potential of taurine supplementation.

Capping dietary starch: Protein ratios enhances performance of broiler chickens offered reduced-crude protein, maize-based diets

The objective of this study was to determine if capping dietary starch:protein ratios in reduced-crude protein diets enhances growth performance of broiler chickens offered maize-based diets. A total of 288 off-sex, male Ross 308 chickens were offered a 2 × 3 factorial array of dietary treatments from 7 to 35 days post-hatch. Dietary starch:protein ratios were either standard (mean: 2.47) or capped (mean: 2.12) with three dietary crude protein concentrations of 195, 185 and 175 g/kg. Dietary starch:protein ratios were capped by substituting soybean meal with full-fat soy; sourced from the same supplier. The parameters assessed included growth performance, relative abdominal fat-pad weights, nutrient utilisation, excreta nitrogen concentrations, distal jejunal and distal ileal digestibility coefficients and disappearance rates of starch and protein, jejunal and ileal starch:protein disappearance rate ratios, distal jejunal and distal ileal apparent amino acid digestibility coefficients, distal ileal amino acid disappearance rates and free amino acid concentrations in systemic plasma. Capping dietary starch:protein ratios significantly reduced ileal starch:protein disappearance rate ratios in birds offered 195, 185 and 175 g/kg crude protein by 14.6% (2.40–2.05), 13.8% (2.61–2.25) and 29.3% (3.75–2.65), respectively. Capping starch:protein ratios in 175 g/kg crude protein diets significantly improved weight gain by 3.45% (2398 versus 2318 g/bird) and feed conversion ratio by 3.75% (1.360 versus 1.413) and relative abdominal fat-pad weights were numerically lighter by 10.3% (11.47 versus 12.78 g/kg). Condensing ileal starch:protein disappearance rate ratios were quadratically related (P < 0.001) to improvements in weight gain (r = 0.740), feed conversion ratio (r = 0.786) and lighter fat-pad weights (r = 0.650). Reducing dietary crude protein concentrations depressed apparent ileal digestibility coefficients of 15 of the 16 amino acids assessed (P = 0.021 to < 0.001); average coefficients were reduced by 6.74% (0.803 versus 0.861). These compromised amino acid digestibilities probably contributed to the 6.43% inferior weight gains (2358 versus 2520 g/bird; P < 0.001) and 3.05% inferior feed conversion ratio (1.387 versus 1.346; P < 0.001) following the dietary crude protein reduction from 195 to 175 g/kg. A better comprehension of the impacts of reduced crude protein diets on endogenous amino acid flows and accumulations of microbial amino acids in distal ileal digesta needs to be achieved as both factors will influence apparent amino acid digestibility coefficients. Finally, capping dietary starch:protein ratios in 175 g/kg crude protein diets showed distinct promise in this study as both weight gain and FCR were significantly enhanced.

Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs: A multi-phase preclinical study

L-asparaginase is a frequently used drug in the treatment of canine malignant lymphoma. Since production and availability of native E. coli-derived L-asparaginase are limited, PEG-L-asparaginase (PEG-ASP) is an alternative. However, recommended doses and dosing intervals are mainly empirically determined. A multi-phase clinical dose-finding study with seven healthy Beagle dogs was conducted to find the minimum effective dose and, potentially, a dosing interval for PEG-ASP in dogs. Plasma concentrations of amino acids and PEG-ASP activity were measured at various time points after administration of different doses of PEG-ASP. Anti-PEG and anti-asparaginase antibody titres were measured.Administration of 10 IU/kg PEG-ASP resulted in asparagine depletion in all dogs, albeit for various durations: for 9 days in all dogs, 15 days in five dogs, 21 days in three dogs and 29 days in one dog. Asparagine suppression occurred at PEG-ASP plasma concentrations < 25 IU/L. Subsequent administrations of a second and third dose of 20 IU/kg and 40 IU/kg PEG-ASP resulted in asparagine suppression at < 9 days in five dogs, accompanied by the development of antibodies against PEG and L-asparaginase. Two dogs with prolonged asparagine suppression after the second and third administration did not develop antibodies. Marked individual variation in the mechanism and duration of response to PEG-ASP was noted. Antibody formation against PEG-ASP was frequently observed and sometimes occurred after one injection. This study suggests that PEG-ASP doses as high as the currently used dose of 40 IU/kg might not be needed in treatment of canine malignant lymphoma.

P-047 The effects of dietary branched-chain amino acids on mice semen parameters and plasma amino acids profile

Abstract Study question Are there any differences between the effect of each member of the branched-chain amino acids (BCAAs) on sperm parameters and plasma amino acids profile? Summary answer Valine supplementation had destructive effects on sperm parameters and viability. However, blood amino acids profile were similar among treatments. What is known already BCAAs, a group of three essential amino acids, have a crucial role on protein synthesis, besides being strongly associated with impaired glucose and fat metabolism. Although BCAAs supplements are one of the most demanding products for the fitness industry to increase the lean body mass and boost exercise performance, little information exists on the advantages and disadvantages of dietary BCAAs on male fertility. Study design, size, duration Fifty NMRI mature male mice were divided into five groups and were fed diets as follow: Control (CTR): 2.4% Beta-alanine, Leucine (Leu): 1.18% Leu + 1.2% Beta-alanine, Isoleucine (Ile): 0.58% Ile + 1.8% Beta-alanine, Valine (Val): 0.65% + 1.7% Beta-alanine, and BCAAs (Leu:Ile:Val ratio of 2:1:1): 2.4% BCAA: 1.18% Leu + 0.58% Ile + 0.65% Val. After 5 weeks, testes and epididymides were dissected, and sperm parameters and plasma amino acids profile were assessed. Participants/materials, setting, methods Semen parameters were evaluated by a Computer-Aided Semen Analysis (CASA) system. Plasma amino acids concentrations were determined by HPLC. Data were analyzed using SPSS and statistical differences among various groups were determined by ANOVA and Tukey’s post-hoc test. Main results and the role of chance Higher BCAAs intake, particularly Val, increased the destructive mechanisms on sperm viability. The results showed no significant difference on body weight after 40 days. Sperm concentration (8.4 vs. 4.5 ×106), progressive motility (51.5 vs. 27.2 %), and viability (67 vs. 56 % for CTR and Val group, respectively) decreased dominantly in the Val group compared to CTR (p≤0.05). The immotile parameter was significantly higher in the Val group compared to the CTR (p≤0.05). In addition, there were no significant differences on plasma amino acids profile. Limitations, reasons for caution The current study's limitation is that only one level of BCAAs was used. Given the potential role of Val on sperm cell death, further data on different levels of all BCAAs, especially Val administration and evaluation of the related mechanisms are needed. Wider implications of the findings The findings of our study show, for the first time, that individual levels of Ile and Leu have different effects on sperm parameters compared with all BCAAs or Val. More attention should be given to BCAAs supplementation and semen quality that was previously ignored. Trial registration number not applicable

The Effect of Mild Renal Dysfunction on the Assessment of Plasma Amino Acid Concentration and Insulin Resistance in Patients with Type 2 Diabetes Mellitus.

Background An increase in the levels of branched-chain amino acids (BCAAs) and certain aromatic amino acids, such as alanine, in plasma is correlated with insulin resistance (IR) in type 2 diabetes mellitus (T2DM). T2DM is a leading risk factor for chronic kidney disease. Meanwhile, renal dysfunction causes changes in plasma amino acid levels. To date, no study has examined how mild renal dysfunction and IR interact with plasma amino acid levels. This study examines the effects of IR and renal dysfunction on plasma amino acid concentrations in T2DM. Methods Data were collected from healthy male participants (controls) and male patients with T2DM between May 2018 and February 2022. Blood samples were collected after overnight fasting. IR and renal function were evaluated using the homeostasis model assessment of IR (HOMA-IR) and serum cystatin C (CysC), respectively. Results A total of 49 and 93 participants were included in the control and T2DM groups, respectively. In the T2DM group, eight amino acids (alanine, glutamic acid, glutamine, glycine, isoleucine, leucine, tyrosine, and valine) and total BCAA showed a significant correlation with HOMA-IR (p < 0.01), whereas six amino acids (γ-aminobutyric acid, citrulline, cysteine, glycine, methionine, and valine) and total BCAA showed a significant correlation with 1/CysC (p < 0.02). However, only alanine, glutamic acid, and each BCAA showed significant differences between the control group and the IR T2DM subgroup. Increases in the BCAA levels with T2DM were canceled by renal dysfunction (CysC ≥ 0.93) in patients with intermediate IR. Conclusion To use plasma BCAA concentration as a marker of IR, renal function must be considered, even in mild renal dysfunction. Increased alanine and glutamic acid levels indicate IR, regardless of mild renal dysfunction.

Comparison of Amino Acid Concentrations in Plasma and Dried Blood Spot Samples Using LC-MS/MS

Background: Dried blood spot samples are suitable for diagnosing some congenital errors of metabolism; however, they provide limited benefit in the regular monitoring of amino acids. Objectives: The present study aimed to evaluate alanine (Ala), arginine (Arg), citrulline (Cit), glutamic acid (Glu), glycine (Gly), isoleucine (Ileu), leucine (Leu), methionine (Met), ornithine (Orn), phenylalanine (Phe), tyrosine (Tyr), and valine (Val) amino acid concentrations in dried blood and plasma samples obtained simultaneously. Methods: Amino acid concentrations were determined in the plasma, and dried blood spot samples obtained simultaneously from 145 patients (50 females and 95 males). Amino acid concentrations in the plasma and dried blood spot samples were studied by LC-MS/MS using original kits. Results: There were significant differences between dried blood spots and plasma in all amino acid concentrations, except for Met and Val. Bland-Altman analysis revealed the highest mean differences in Glu (-148.1), Gly (-70.1), and Ala (-58.1). Deming regression analysis showed that plasma and dried blood spot samples were consistent concerning Cit, Met, Phe, and Tyr concentrations. Conclusions: Differences in methodology and sample can influence amino acid concentrations. Dried blood spot samples might cause errors in amino acid screening programs.

Mild Cognitive Impairment Is Associated With Markers of Muscle Weakness and Reduced Bone Density, and Specific Metabolic Alterations Despite Preserved Physical Activity

ObjectivesBone loss and frailty commonly occur in people with dementia residing in nursing homes and lead to increased risk of disabilities and poor health outcomes. Whether these systemic manifestations and related metabolic disturbances are present in older adults with Mild Cognitive impairment (MCI), who are still physically active, remains unclear. MethodsCommunity dwelling older adults without confounding comorbidities were divided, using the Montreal Cognitive Assessment (MoCA) score cut-off of 26, into two groups: non-MCI (n = 18; age: 67.3 [63.3, 71.2 y]) and MCI (n = 20; age: 71.3 [66.9, 75.7 y]). Body composition (by DXA), respiratory strength (by mouth pressure), and extremity strength (by dynamometer) were assessed. Stable isotope techniques were used to measure production and plasma concentrations of amino acids involved in muscle, bone, and brain health (tau-methylhistidine, hydroxyproline, glycine, tryptophan). Plasma enrichments were analyzed by LC-MS/MS. Statistics performed by ANCOVA with age, gender, and BMI as covariates. Significance set at P < 0.05. Results expressed as means [95% CI]. ResultsMCI participants (MoCA score: 22.5 [21.3, 23.6]) had lower respiratory muscle strength (p = 0.007) than the non-MCI group (MoCA score: 28.2 [27.5, 28.8]) but muscle mass and daily physical activity were not different. Bone density of the spine (p = 0.02) and hip (p = 0.07) were lowest in those with the lowest MoCA scores. The MCI group had lower concentrations of glycine (p = 0.0045), tryptophan corrected for large neutral amino acids (p = 0.0017), and productions of glycine (p = 0.0085), tau-methylhistidine (p = 0.05), and tryptophan (p = 0.06). MoCA score was negatively associated with plasma triglyceride (p = 0.02) and liver enzyme (AST) level (p = 0.01), but not with glucose or CRP levels. ConclusionsOlder adults with MCI are prone to low bone density and respiratory muscle weakness despite preserved physical activity. Whether these systemic manifestations are causally related to the observed metabolic alterations in MCI deserves further investigation. Funding SourcesNone

The Role of Comorbidities on Aging-Induced Changes in Muscle Health and Amino Acid Kinetics

ObjectivesAging and comorbidities are known to influence amino acid metabolism, contributing to reduced muscle and cognitive dysfunction in older adults. Whether these aging-induced manifestations remain after correction for the presence of comorbidities is unclear. MethodsOlder adults were selected from the MEDIT database. The subjects were divided into two age groups: 264 young old (age 50–70 y: n = 149 with at least 1 comorbidity based on Charlson comorbidity index (CCI > 0) and n = 115 with CCI = 0), and 196 middle old (age 70–85 y: n = 119 with CCI > 0 and n = 77 with CCI = 0). Body composition was assessed by DXA, respiratory and skeletal muscle strength by mouth pressures and dynamometry, and cognition and mood by assessments and questionnaires. Postabsorptive kinetics of multiple amino acids were measured by pulse stable isotope administration and subsequent blood sampling. Plasma amino acid concentrations and enrichments were analyzed by LC-MS/MS to measure whole-body protein production (WBP) and conversion rates. Statistics are done with ANCOVA with sex and BMI and age group as independents. Results expressed as means [95% CI]. ResultsThe middle old had lower lean mass on whole body level and in the extremities (p < 0.0001), and lower respiratory (p = 0.05) and handgrip (p = 0.005) strength compared to the young old, independent of muscle health lowering effects of CCI. Although no differences were observed in cognition and mood between the groups, an age x CCI interaction was found for depression, anxiety (p = 0.03), and lean mass extremity (p = 0.04). The middle old had lower values for WBP of tau-methylhistidine (p = 0.01), hydroxyproline (P = 0.008), and taurine (p = 0.004), and plasma glutamine concentration (P = 0.016). In addition, the middle old showed higher glutamine to glutamate conversion (p = 0.02). Age x CCI interaction was observed for plasma concentration of tyrosine (p = 0.04). No differences were observed in plasma concentrations and WBP of phenylalanine and the branched-chain amino acids (leucine, valine, and isoleucine) between the groups. ConclusionsMuscle loss and weakness and specific disturbances in amino acid kinetics due to aging exist even after correction for the presence of comorbidities. Funding SourcesNone

Prediabetes Is Associated with Specific Changes in Valine Metabolism

ObjectivesRecent studies have suggested that a high plasma concentration of the branched-chain amino acids (BCAAs) can serve as a biomarker for type-2-diabetes (T2D). Whether this is also the case for prediabetes remains unclear. Our goal is to examine whether specific disturbances exist in the kinetics of the BCAAs leucine, isoleucine and valine in middle aged/older adults with prediabetes. MethodsWe measured BCAA kinetics in 70 prediabetic subjects (fasting glucose: 5.7-6.5 mM), 47 diabetic subjects (fasting glucose: ≥6.5 mM, or are taking medication to control blood glucose) and 170 healthy subjects (fasting glucose: < 5.7 mM) that were 40 years or older. In the fasted state, a pulse of stable isotopes containing leucine, isoleucine and valine was administered intravenously while blood was sampled to assess their whole body production rates (WBP). BCAA tracer enrichment and concentration analyses were done by LC-MS/MS. BCAA whole body production rates were calculated from the area under the curve (AUC). Statistics by ANCOVA corrected for age, sex, and lean body mass as covariates. Significance set at P< 0.05. Results expressed as means [95% CI]. ResultsThe subjects with prediabetes had a lower valine WBP (9492 [8256, 10913] vs. 12288 [11247, 13425] μmol/h, P = 0.0021), but a higher plasma valine concentration (185.7 [176.4, 195.6] vs. 172.2 [166.5, 178.1] μM, P = 0.0178) than the healthy control subjects. No differences in WBP or concentrations of isoleucine or leucine were observed between the groups. Diabetic subjects had the highest plasma concentration for valine across the groups (213.8 [200.4, 228.0] μM, P = < 0.0001), but without a change in the WBP of leucine, isoleucine and valine. ConclusionsPrediabetes is characterized by specific changes in the concentration and whole body production of valine. Funding SourcesNone

Increased Amino Acid Turnover and Net Protein Breakdown but Preserved Muscle and Cognitive Function in Obese Middle-Age Adults

ObjectivesSkeletal muscle weakness has been observed in obese patients despite preserved or even greater lean body mass. Additionally, the presence of obesity-related comorbidities is a recognized risk factor for cognitive dysfunction and mood disturbances. Metabolism of several amino acids (AAs) including the Branched-chain Amino Acids (BCAAs) is altered in obesity but whether these disturbances are associated with muscle and cognitive dysfunction remain underexplored.Methods159 subjects were divided, using the BMI cut-off of 30 kg/m2, into two groups: 79 non-obese (32 males/47 females, age 48.5 [43.3, 53.7], BMI 25.2 [24.6, 25.7] kg/m2) and 80 obese (31 males/49 females, age 54.3 [51.0, 57.6], BMI 38.3 [36.9, 39.6] kg/m2). Postabsorptive whole-body production (WBP) rates of several AAs were measured by IV pulse of stable isotopes including BCAAs, Phenylalanine (Phe), Tyrosine (Tyr), Glutamate (Glu), and Tryptophan (Trp). Plasma amino acid enrichments and concentrations were analyzed by LC-MS/MS. Large Neutral Amino Acids (LNAA) was calculated as the sum of BCAAs, Phe, and Tyr. Body composition (DXA), hand and leg peak strength and endurance (isokinetic dynamometer), cognitive function (Stroop, TMT), and mood (POMS, HADS) were assessed. Statistics performed by ANCOVA with age, gender, and lean body mass as covariates. Significance at P < 0.05. Results expressed as means [95% CI].ResultsObese subjects had higher concentrations of plasma Leu (12%, P = 0.0097), Ile (7%, P = 0.0310), Tyr (23%, P < 0.0001), and Glu (40%, P = 0.0001). The obese group was also characterized by elevated WBP of BCAAs (8%, P = 0.0343), Phe (12%, P = 0.0003), Tyr (18%, P = 0.0005) and increased whole-body net protein breakdown (Phe to Tyr conversion, 11%, P = 0.0212). Both groups had similar muscle and cognitive functions but obese individuals had greater scores for self-reported depressive symptoms (P = 0.0273), anger (P = 0.0234), fatigue (P = 0.0098), and tension (P = 0.0158). No changes in Trp metabolism were found but obese subjects had elevated LNAA (7%, P = 0.0170) resulting in increased systemic Trp availability to the brain (P = 0.0014).ConclusionsObese subjects have preserved muscle and cognitive function despite greater whole-body net protein breakdown and increased turnover of several AAs involved in muscle metabolism and serotonin synthesis.Funding SourcesNone.

Plasma Amino Acid Concentrations in Patients with Alcohol and/or Cocaine Use Disorders and Their Association with Psychiatric Comorbidity and Sex.

(1) Background: Co-occurrence of mental and substance use disorders (SUD) is prevalent, but complicates their clinical courses, and specific biomarkers are required. Amino acids are altered in primary mental disorders; however, little is known about SUD and psychiatric comorbidity. Because most psychiatric disorders and biomarkers show sex differences, we investigated amino acids in men and women with alcohol and/or cocaine use disorders (AUD and/or CUD) and psychiatric comorbidity. (2) Methods: A cross-sectional study was conducted in 295 participants, who were divided into four groups (AUD, n = 60; CUD, n = 41; AUD + CUD, n = 64; and control, n = 130). Participants were clinically assessed, and plasma amino acid concentrations were analyzed in relation to sex, diagnosis of SUD and psychiatric comorbidity (3) Results: In the total sample, there were sex differences, and women showed lower Iso, Leu, Gln and Glu than men. While patients with CUD and AUD + CUD had higher Glu, Gly, Orn and Ser than controls, patients with AUD showed no differences. In SUD, patients with psychiatric comorbidity had lower Orn and higher Ala than non-comorbid patients in the AUD group. (4) Conclusions: There was a dysregulation of plasma amino acids in abstinent patients with SUD. However, our results suggest the importance of considering the clinical characteristics and sex in the validity of amino acids as potential biomarkers for SUD.

The acute effects of insect vs. beef-derived protein on postprandial plasma aminoacidemia, appetite hormones, appetite sensations, and energy intake in healthy young men

The purpose of this study was to evaluate the acute effects of ingesting beef- and insect-derived protein on postprandial plasma amino acid and appetite hormone concentrations, appetite sensations, and ad libitum energy intake. In a randomized, double-blind, crossover study, 20 young men (23 (SD: 4) y) completed two trials during which arterialized blood samples and VAS questionnaires were collected at baseline, and over 300-min after ingestion of beverages with similar energy and macronutrient content containing 25 g beef- or insect-derived (cricket) protein. Blood samples were analyzed for plasma amino acid and appetite hormone concentrations, while VAS questionnaires were applied to assess appetite sensations. After each trial, an ad libitum meal was immediately provided to assess energy intake. Adjusted mean postprandial incremental area under the curve (iAUC) was greater for cricket vs. beef-derived protein for plasma leucine, branched-chain amino acid, and essential amino acid concentrations (all P &lt; 0.0001). Adjusted mean postprandial iAUC for hunger was lower following beef (-3030 (SE: 860)) vs. cricket-derived (-1197 (SE: 525)) protein (Difference: -1833 (95% CI: -3358, -308); P = 0.02), but was not different for other appetite sensations or appetite hormones (all P &gt; 0.05). Adjusted mean ad libitum energy intake was 4072 (SE: 292) and 4408 (SE: 316) kJ following beef- and cricket-derived protein (Difference: -336 (95% CI: -992, 320); P = 0.30). Acute ingestion of cricket and beef-derived protein leads to differences in postprandial plasma amino acid concentrations, but elicits similar effects on appetite hormones, appetite sensations, and ad libitum energy intake in young men.

Influence of hempseed cake inclusion on growth performance, carcass characteristics, feeding behavior, and blood parameters in finishing heifers.

As the hemp industry continues to develop in the United States, there is an increasing interest in feeding byproducts of industrial hemp production to livestock. A completely randomized design experiment using crossbred finishing heifers (initial body weight [BW] ± SE = 494 ± 10 kg) was conducted to determine the effects of feeding hempseed cake in a corn-based finishing diet (10% forage) formulated to meet or exceed ruminally degradable and metabolizable protein requirements on growth performance, carcass characteristics, feeding behavior, and plasma parameters. Dietary treatments were the inclusion of 20% (dry matter [DM] basis) of dried corn distillers grains plus solubles (DDGS, n = 16) or hempseed cake (HEMP, n = 15). Cattle were housed in two pens, had ad libitum access to feed and water, and individual intakes and feeding behavior were monitored using the Insentec feeding system. Cattle were fed treatment diets for 111 d, and every 14 d BW were measured and blood samples were collected. Blood plasma was analyzed for glucose, urea nitrogen, and individual amino acids, and results were analyzed using repeated-measures analysis in SAS. Final BW, average daily gain, gain:feed, and hot carcass weight decreased (P ≤ 0.05) by 2.3%, 7.7%, 7.7%, and 2.6%, respectively, in heifers fed the HEMP diet than in heifers fed the DDGS diet. Net energy for maintenance and gain (Mcal/kg of feed, DM basis), estimated based on heifer intake and performance, were greater (P = 0.02) for the DDGS diet than for the HEMP diet. All other performance and carcass characteristics were not different (P ≥ 0.20) between treatments. Heifers fed the HEMP diet had greater (P < 0.05) plasma urea nitrogen concentration in samples from each collection day compared with heifers fed the DDGS diet, although there was a treatment-by-day interaction (P < 0.01) because of variability in the magnitude of treatment differences over time. Plasma glucose concentration was not influenced (P = 0.17) by dietary treatment. Plasma concentrations of total amino acids, nonessential amino acids, and essential amino acids were not different between treatments (P ≥ 0.09), although there were several interactions between treatment and day (P ≤ 0.04) for individual amino acids. These data suggest that hempseed cake has a lower net energy for maintenance and gain relative to DDGS when adequate metabolizable protein is supplied, while still providing adequate nutrition to support the acceptable performance of finishing cattle.