Serum Amino Acid Levels Research Articles

Impact of Dietary Patterns and Serum Amino Acid Profile on Metabolic Syndrome Development in Mexican Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the main endocrine disorder in women of reproductive age worldwide. This condition is often associated with various metabolic alterations that contribute to the development of metabolic syndrome (MetS). Recent research suggests that branched-chain amino acid (BCAA) dysregulation is observed in PCOS. This study aims to investigate the relationship between dietary patterns, body composition, metabolic analytes, and serum amino acid levels in Mexican women with PCOS. Utilizing a cross-sectional design, we found that both study groups, PCOS (n = 24) and PCOS + MetS (n = 21), exhibited increased relative fat mass and dietary habits characterized by high simple sugar intake and low protein consumption, correlating with levels of relative fat mass and leptin. Notably, serum concentrations of BCAAs and glutamic acid were significantly elevated in the PCOS + MetS group. Our findings suggest that a metabolic approach may enhance the prediction and management of MetS in women with PCOS, highlighting the importance of dietary interventions in this population.

Associations of Amino Acids with the Risk of Prediabetes: A Case-Control Study from Kazakhstan.

The high global prevalence of prediabetes requires its early identification. Amino acids (AAs) have emerged as potential predictors of prediabetes. This study investigates the association between amino acids and prediabetes in the Kazakh population. In this case-control study, serum AAs levels were measured using the Trace GC 1310 gas chromatography system coupled with the TSQ 8000 triple quadrupole mass spectrometer (Thermo Scientific, Austin, TX, USA) followed by silylation with the BSTFA + 1% TMCS derivatization method. Biochemical parameters, including total cholesterol, HDL-C, LDL-C, triglycerides, fasting glucose, HbA1c, and Creatinine, were assessed for each participant. Trained professionals conducted anthropometric and physical examinations (which included taking blood pressure and heart rate measurements) and family history collection. A total of 112 Kazakh individuals with prediabetes and 55 without prediabetes, aged 36-65 years, were included in the study. Only Alanine and valine showed a significant association with prediabetes risk among the 13 AAs analyzed. Our findings revealed an inverse relationship between Alanine and Valine and prediabetes in individuals of Kazakh ethnicity. A lower serum level of Alanine and Valine may serve as a predictive biomarker for prediabetes in the Kazakh population.

A whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer.

Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. Here, we investigated the impact of a whole food, plant-based diet on lowering the serum levels of amino acids in patients with cancer. Patients with metastatic breast cancer (n=18) were enrolled in clinical trial NCT03045289 . An ad libitum whole food, plant-based diet was implemented for 8 weeks without calorie or portion restriction. We found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF-1 were reduced in participants. The diet contained lower levels of essential and non-essential amino acids. Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids). These findings provide a tractable approach to limiting amino acid levels in cancer patients. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities.

Maternal cafeteria diet programs fecal microbiota and modulates serum fatty acid and amino acid levels in adulthood rats

Maternal food environment can program fecal microbiota in offspring mediated by the imprint of intrauterine conditions. Gut bacteria play a role in host fatty acid and amino acid metabolism. This study aimed to determine the effects of maternal diet on fecal microbiota, and the impact on fatty acid and amino acid metabolism in male offspring rats. Ten male pups from dams fed standard diet (C-C, n = 5) and cafeteria diet (Caf-C, n = 5) were fed standard chow diet for twenty-three weeks. Fresh fecal samples were collected at three and twenty-six weeks of age for fecal microbiota analysis by metagenomic sequencing of the V3-V4 region of the 16S rRNA gene. At the end of the study, serum samples were collected to analyse fatty acids from phospholipid and cholesterol ester fractions by gas chromatography and free amino acids by liquid chromatography. The bacterial abundance from the Actinobacteria and Proteobacteria phyla significantly decreased over time for both groups. Additionally, significant differences were found between C-C and Caf-C groups in these bacterial phyla. In the Caf-C group, Firmicutes and Elusimicrobia phyla increased, while Bacteroidetes decreases in adulthood samples. At the genus level, the abundance of Bacteroides decreased, while Elusimicrobium, Lactobacillus, Turicibacter, Blautia, and Veillonella increased in the Caf-C group. Several metabolites including PL-MCFAs (caprylic acid and capric acid), CE-MUFAs (palmitoleic acid and heptadecenoic acid), and free amino acids aspartate, glutamic acid, and cysteine were significantly higher in Caf-C group. This study underscores the putative programming of offspring fecal microbiota by maternal diet impact. These changes led to alterations fatty acids and amino acids metabolism in adult male offspring rats.

Study on the difference and clinical value of serum amino acids in patients with laryngeal squamous cell carcinoma

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry（HPLC-MS） was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group（P<0.05）. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group（P=0.024）. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ（P=0.026）. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma（P=0.041）. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old（P=0.033）. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history（P=0.033）. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption（P=0.003）. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma（AUC=0.855）. However, citrulline alone had the highest specificity（0.830） in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group（P<0.001）. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.

Exploring altered free amino acids and metabolites: Insights into the metabolic landscape of preeclampsia

IntroductionPreeclampsia (PE) is a complex disease that poses a risk for maternal and perinatal morbidity and mortality. This study aimed to investigate the role of maternal serum amino acids (AAs) levels in PE. Materials and methodsA total of 56 pregnant women (26 with PE and 30 controls) were included in the study. The participants had a confirmed gestational age between 24 and 37 weeks. The mean body mass index (BMI) for the PE group was 33.1 kg/m2, while the control group had a mean BMI of 29.6 kg/m2. AAs levels were quantified, and statistical analyses were performed to identify significant differences between the two groups. Receiver Operating Characteristic (ROC) curve analysis was employed the diagnostic potential of specific AAs. ResultsWe observed significantly elevated levels of multiple AAs in the PE group, including citrulline, lysine, ethanolamine, ornithine and histidine. Citrulline exhibited exceptional predictive power for PE with 100.0% sensitivity and specificity at a cutoff of 7.79 µmol/L, reflected in an area under the curve (AUC) of 1.000. DiscussionOur study highlights the crucial involvement of altered amino acid levels, specifically in the urea cycle, disruptions in lysine and ethanolamine metabolism in PE development. Exploring these changes may reveal new therapeutic targets, providing insights into the disease's molecular mechanisms. Understanding amino acid metabolism in PE not only informs therapeutic strategies but also holds the potential to revolutionize early diagnosis and intervention.

Targeted metabolomic profiles of serum amino acids are independently correlated with malnutrition in older adults.

Malnutrition is a common geriatric syndrome that is closely associated with adverse clinical outcomes and poses significant harm to older adults. Early assessment of nutritional status plays a crucial role in preventing and intervening in cases of malnutrition. However, there is currently a lack of measurable methods and biomarkers to evaluate malnutrition in older adults accurately. The aim of this study is to investigate the independent correlation between serum levels of amino acids and malnutrition in older adults, and to identify effective metabolomics biomarkers that can aid in the early detection of geriatric malnutrition. A total of 254 geriatric medical examination participants from Beijing Hospital were included in the study, consisting of 182 individuals with normal nutritional status (Normal group) and 72 patients at risk of malnutrition or already malnourished (MN group). Malnutrition was assessed using the Mini-Nutritional Assessment Short-Form (MNA-SF). Demographic data were collected, and muscle-related and lipid indexes were determined. Serum amino acid concentrations were measured using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation between serum amino acid levels and malnutrition was analyzed using non-parametric tests, partial correlation analysis, linear regression, and logistic regression. The geriatric MN group exhibited significantly lower serum aromatic amino acid levels (P < 0.05) compared to the normal group. A positive correlation was observed between serum aromatic amino acid levels and the MNA-SF score (P = 0.002), as well as with known biomarkers of malnutrition such as body mass index (BMI) (P < 0.001) and hemoglobin (HGB) (P = 0.005). Multivariable logistic or linear regression analyses showed that aromatic amino acid levels were negatively correlated with MN and positively correlated with the MNA-SF score, after adjusting for some confounding factors, such as age, gender, BMI, smoking status, history of dyslipidemia, diabetes mellitus and frailty. Stratified analyses revealed that these trends were more pronounced in individuals without a history of frailty compared to those with a history of frailty, and there was an interaction between aromatic amino acid levels and frailty history (P = 0.004). Our study suggests that serum aromatic amino acids are independently associated with malnutrition in older adults. These results have important implications for identifying potential biomarkers to predict geriatric malnutrition or monitor its progression and severity, as malnutrition can result in poor clinical outcomes.

Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders.

Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in theUK Biobank participants (117944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine. Our gene-based analysis mapped 46-293 genes associated with serum amino acids, including MIP,GLS2, SLCgene family, GCKR, LMO1, CPS1and COBLL1.The gene-property analysis across 30 tissues highlighted enriched expression of the identified genes in liver tissues for all studied amino acids, except for isoleucine and valine, in muscle tissues for serum alanine and glycine, in adrenal gland tissues for serum isoleucine and leucine, and in pancreatic tissues for serum phenylalanine. Mendelian randomization (MR) phenome-wide association studyanalysis and subsequent two-sample MR analysis provided evidence that every standard deviation increase in valine is associated with 35% higher risk of type 2 diabetes and elevated levels of serum alanine and branched-chain amino acidswith higher levels of total cholesterol, triglyceride andlow-density lipoprotein, and lower levels ofhigh-density lipoprotein. In contrast to reports by observational studies, MR analysis did not support a causal association between studied amino acids and coronary artery disease, Alzheimer's disease, breast canceror prostate cancer. In conclusion, we explored the genetic architecture of serum amino acids and provided evidence supporting a causal role of amino acids in cardiometabolic health.

Gut flora metagenomic analysis coupled with metabolic and deep immune profiling in chronic kidney disease.

Perturbation of gut microbiota has been linked to chronic kidney disease (CKD), which was correlated with a sophisticated milieu of metabolic and immune dysregulation. To clarify the underlying host-microbe interaction in CKD, we performed multi-omics measurements, including systems-level gut microbiome, targeted serum metabolome and deep immunotyping, in a cohort of patients and non-CKD controls. Our analyses on functional profiles of the gut microbiome showed a decrease in the diversity and abundance of carbohydrate-active enzyme (CAZyme) genes but an increase in the abundance of antibiotic resistance, nitrogen cycling enzyme and virulence factor genes in CKD. Moreover, models generated using measurements of serum metabolites (amino acids, bile acids and short-chain fatty acids) or immunotypes were predictive of renal impairment but less so than many of the functional profiles derived from gut microbiota, with the CAZyme genes being the top-performing model to accurately predict the early stage of diseases. In addition, co-occurrence analyses revealed coordinated host-microbe relationships in CKD. Specifically, the highest fractions of significant correlations were identified with circulating metabolites by several taxonomic and functional profiles of gut microbiome, while immunotype features were moderately associated with the abundance of microbiome-encoded metabolic pathways and serum levels of amino acids (e.g. B cell cluster tryptophan and B cell cluster tryptophan metabolism). Overall, our multi-omics integration revealed several signatures of systems-level gut microbiome in robust associations with host-microbe co-metabolites and renal function, which may have aetiological and diagnostic implications in CKD.

Association between serum trace element, mineral, and amino acid levels with non-alcoholic fatty liver disease (NAFLD) in adult women

The objective of the present study is assessment of serum trace element and amino acid levels in non-alcoholic fatty liver disease (NAFLD) patients with subsequent evaluation of its independent associations with markers of liver injury and metabolic risk. Materials and methods140 women aged 20–90 years old with diagnosed NAFLD and 140 healthy women with a respective age range were enrolled in the current study. Analysis of serum and hair levels of trace elements and minerals was performed with inductively-coupled plasma mass-spectrometry (ICP-MS). Serum amino acid concentrations were evaluated by high-pressure liquid chromatography (HPLC) with UV-detection. In addition, routine biochemical parameters including liver damage markers, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT), were assessed spectrophotometrically. ResultsThe findings demonstrated that patients with NAFLD were characterized by higher ALT, GGT, lactate dehydrogenase (LDH) and cholinesterase (CE) activity, as well as increased levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and uric acid. NAFLD patients were characterized by reduced serum and hair Co, Se, and Zn levels, as well as hair Cu content and serum Mn concentrations in comparison to controls. Circulating Ala, Cit, Glu, Gly, Ile, Leu, Phe, and Tyr levels in NAFLD patients exceeded those in the control group. Multiple linear regression demonstrated that serum and hair trace element levels were significantly associated with circulating amino acid levels after adjustment for age, BMI, and metabolic parameters including liver damage markers. ConclusionIt is proposed that altered trace element handling may contribute to NAFLD pathogenesis through modulation of amino acid metabolism.

Maternal serum amino acid levels as predictors of premature rupture of membranes: A comprehensive analysis

IntroductionThe aim of this study is to investigate the association between altered maternal serum amino acids (AAs) levels and premature rupture of membranes (pPROM) in pregnant women. MethodsWe conducted a case-control study involving 60 pregnant women diagnosed with pPROM and 60 healthy pregnant women as controls. Amino acid levels were quantified using high-performance liquid chromatography. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive capability of specific AAs for pPROM. ResultsOur findings revealed that lysine, glycine, and glutamic acid levels were significantly elevated in the pPROM group compared with the control group. Lysine, with a threshold value exceeding 137.90 μmol/L, exhibited the highest predictive accuracy, with an area under the curve (AUC) of 0.796 (p < 0.001), sensitivity of 66.7 %, and specificity of 80.0 %. Glycine, with a cut-off value of >242.48 μmol/L, had an AUC of 0.789 (p < 0.001), sensitivity of 83.3 %, and specificity of 65.0 %. Glutamic acid, at a threshold of 111.40 μmol/L, demonstrated an AUC of 0.787 (p < 0.001), sensitivity of 88.3 %, and specificity of 65.0 %. These AAs could effectively predict the occurrence of pPROM. ConclusionElevated blood levels of lysine, glycine, and glutamic acid were found to be associated with pPROM. These AAs serve as potential predictive biomarkers for pPROM, with lysine showing the highest AUC and sensitivity. Identifying such biomarkers may contribute to the development of non-invasive diagnostic tools for pPROM risk assessment, enabling timely interventions and improved maternal and fetal outcomes.

Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson's disease after dietary supplementation with branched-chain amino acids.

The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial-gut-brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson's disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography-mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

Predictive Ability of Serum Amino Acid Levels to Differentiate Fibromyalgia Patients from Healthy Subjects.

Fibromyalgia is a complex illness to diagnose and treat. To evaluate a broad range of circulating free amino acid (AA) levels in fibromyalgia patients as well as the ability of the AAs to differentiate fibromyalgia patients from healthy subjects. We carried out a case-control study to evaluate AA levels in 62 patients with fibromyalgia and 78 healthy subjects. This study adheres to the STROBE guidelines. AAs content was assayed by HPLC in serum samples. The predictive value of AA levels in fibromyalgia was determined by receiver operating characteristic (ROC) curve and forward binary logistic regression analyses. Fibromyalgia patients showed higher serum levels of aspartic acid, glutamic acid, aminoadipic acid, asparagine, histidine, 3-methyl-histidine, 5-methyl-histidine, glycine, threonine, taurine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, ornithine, lysine, branched chain AAs (BCAAs), large neutral AAs, essential AAs (EAAs), non-essential AAs (NEAAs), basic AAs, EAAs/NEAAs ratio, phenylalanine/tyrosine ratio, and global arginine bioavailability ratio than the controls. Serum alanine levels were lower in patients than in controls. According to ROC analysis, most of these AAs may be good markers for differentiating individuals with fibromyalgia from healthy subjects. Results of logistic regression showed that the combination of glutamic acid, histidine, and alanine had the greatest predictive ability to diagnose fibromyalgia. Our results show an imbalance in serum levels of most AAs in patients with fibromyalgia, which suggest a metabolic disturbance. The determination of serum levels of these AAs may aid in the diagnosis of fibromyalgia, in combination with clinical data of the patient.

Relationship between serum amino acid levels and acne severity

AimAcne is a common skin disease in which metabolic factors have been suggested to play a role in its pathogenesis. The aim of this study was to evaluate the relationship between serum amino acid levels and acne and acne scar development. Material and methodsIn this cross-sectional study, 30 patients with scatricial acne, 30 patients with non-scatricial acne and 30 healthy subjects were included. Global acne scores and scar scores were calculated. Venous blood samples of the participants were analyzed by liquid chromatography-tandem mass spectrometry and serum levels of a total of 24 amino acids including nine essential amino acids, 11 nonessential amino acids and four other amino acids were measured. ResultsSerum levels of the branched chain amino acids leucine, isoleucine and valine were significantly higher in the cicatricial acne group (p: <0.001, 0.001, <0.001, respectively) and in the non-cicatricial acne group (p: 0.039, 0.045, 0.001, respectively) compared to healthy subjects. There were also significant positive correlations between the levels of these amino acids and global acne scores (p = 0.048, r = 0.255, p = 0.006, r = 0.354, p = 0.017, r = 0.307, respectively) and scar scores (p = 0.032, r = 0.392, p = 0.021, r = 0.424, p = 0.018, r = 0.427, respectively). Serum tryptophan levels were significantly lower in both scatricial and non-scatricial acne groups compared to healthy subjects (p = 0.033 and < 0.001, respectively). ConclusionImpaired metabolism of branched-chain amino acids and tryptophan may be associated with acne pathogenesis, acne severity and scarring.

Vitamin D Supplementation Influences Ultramarathon-Induced Changes in Serum Amino Acid Levels, Tryptophan/Branched-Chain Amino Acid Ratio, and Arginine/Asymmetric Dimethylarginine Ratio.

Exercise affects serum levels of amino acids and their metabolites, with important metabolic consequences. Since vitamin D impacts skeletal muscle protein degradation, we hypothesised that it would also impact exercise-induced changes in serum amino acid levels and the serum levels of arginine metabolites, influencing the body's ability to synthesise NO. Accordingly, we analysed the effect of a single high-dose vitamin D supplementation on the serum levels of various amino acids in ultramarathon runners. Thirty-five male amateur runners were assigned to the supplemented group, administered 150,000 IU vitamin D in vegetable oil 24 h before the run (n = 16), or the control (placebo) group (n = 19). Blood was sampled 24 h before, immediately after, and 24 h after the run. Changes in the serum levels of some amino acids were distinct in the two groups. The asymmetric dimethyl arginine levels were significantly decreased immediately after the run and increased 24 h later and were not affected by the supplementation. The symmetric dimethyl arginine levels were increased after the run in both groups but were lower in the supplemented group than in the placebo group 24 h after the run. The dimethylamine levels increased significantly in the supplemented group as compared to the placebo group. In conclusion, vitamin D impacts exercise-induced changes in serum amino acids and methylated arginine metabolites.

Influence of lactic-acid bacteria feed supplementation on free amino acid levels in serum and feces of rainbow trout (Oncorhynchus mykiss, Walbaum 1792)

IntroductionThe influence of intestinal microbiota, particularly lactic-acid bacteria, on digestion and nutrient metabolic activities has been extensively studied. In this research, we investigated the effects of supplementing the feed of rainbow trout (O. mykiss) with P. acidilactici or L. lactis probiotics. A Control group without probiotic supplementation was also included. The study aimed to evaluate growth, feed conversion indices, free amino acid levels in serum and feces, and the relative gene expression of amino acid solute carrier transporters (SLC).MethodsRainbow trout weighing 73.9±10 g were fed with a basal commercial diet supplemented with mono-strains of P. acidilactici or L. lactis at a dosage of 5 x 108 CFU per gram of feed for 60 days. The trout were reared in 100-liter tanks with independent closed recirculation systems, with a water replacement rate of 80% of the total volume daily and a controlled temperature of 15 ± 0.3 °C. The proximate composition of the basal diet consisted of crude protein (49.8%), fat (32.1%), fiber (1.31%), ash (13%), and moisture (8.3%) on a dry matter basis. The diet was provided at a rate of 2% of bodyweight per day.ResultsNo significant differences (p &amp;gt; 0.05) were observed in growth and feed conversion indices between the experimental groups. However, significant differences in free amino acid levels in feces and serum samples (p ≤ 0.05) were observed. The P. acidilactici group exhibited significantly higher levels of glutamate, lysine, proline, and tyrosine in feces samples, and higher levels of arginine, iso/leucine, phenylalanine, proline, serine, threonine, and valine in serum samples compared to the Control group. Additionally, the supplemented probiotic groups showed significant downregulation (p ≤ 0.05) of theslc6a19 and slc7a9 genes, which encode transporters for neutral and cationic amino acids.DiscussionThe autochthonous rainbow trout strain, P. acidilactici, demonstrated more pronounced effects on amino acid levels in feces and serum compared to the non-autochthonous L. lactis strain. However, the increased amino acid levels, particularly in the serum, resulting from P. acidilactici supplementation, did not lead to improved trout growth or feed conversion. Nonetheless, lactic-acid bacteria supplementation induced measurable metabolic effects, as evidenced by elevated levels of specific amino acids in the serum and feces.Future research should focus on evaluating these probiotic effects using specialized diets and considering the observed metabolic effects in this study.

Glucagon cell hyperplasia and neoplasia: a recently recognized endocrine receptor disease.

Glucagon cell hyperplasia and neoplasia (GCHN) is the name of an endocrine receptor disease, whose morphology was first described in 2006. Three years later this rare disease was found to be to be caused by an inactivating mutation of the glucagon receptor (GCGR) gene. Functionally, the genetic defect mainly affects glucagon signaling in the liver with changes in the metabolism of glycogen, fatty acids and amino acids. Recent results of several studies in GCGR knockout mice suggested that elevated serum amino acid levels probably stimulate glucagon cell hyperplasia with subsequent transformation into glucagon cell neoplasia. This process leads over time to numerous small and some large pancreatic neuroendocrine tumors which are potentially malignant. Despite high glucagon serum levels, the patients develop no glucagonoma syndrome. In 2015 GCHN was identified as an autosomal recessive hereditary disorder.

Transpulmonary amino acid metabolism in the sugen hypoxia model of pulmonary hypertension

Background: Pulmonary arterial hypertension (PAH) is characterized by narrowing of the pulmonary arteries, endothelial cell dysfunction, and an increased vascular cell proliferation. Increased proliferation is also accompanied by glycolytic shift, where glucose is shunted towards anaerobic respiration and production of critical macromolecules. This decreases the available glucose that can be used as a fuel in the tricarboxylic acid (TCA) cycle. To compensate for the lack of TCA cycle metabolites, there is an increase in the use of non-glucose fuels - such as amino acids and fatty acids. However, the effect of this shift on other metabolic pathways is still unknown. In this study, we investigated the levels of metabolites across the pulmonary circulation to define the metabolic shift that cells undergo during PAH. Material &amp; Methods: We carried out metabolomic analysis on serum samples taken from the right and left ventricles (RV and LV) of rats with PAH (SU5416/Hypoxia model: SuHx) and normoxic controls. We also isolated MVECs from each group and performed both targeted and untargeted metabolomics on the cell lysates. Results: Induction of PAH resulted in increased pulmonary artery pressures and RV hypertrophy. Metabolomics of the RV serum were different in PAH versus control rats. This was driven by lower metabolite levels of several amino acids, including glutamine, phenylalanine, and valine. Normoxia- and SuHx-MVEC lysates samples were also distinct, with increased levels of lactic acid contributing significantly to the differences between animals with PAH and controls. Importantly, and in contrast to the serum, where glutamine levels were decreased, we observed increased levels of intracellular glutamine in our analysis. Similarly, intracellular levels of amino acids like phenylalanine, tyrosine and leucine were increased in these lysates. This also contrasted with the serum, where levels of these amino acids were decreased. Interestingly, LV levels of amino acids like valine, glutamine and lysine were similar in normoxic and SuHx samples. However, we did observe increased citrulline levels in SuHx LV serum samples. Comparing the LV/RV ratio in our samples revealed that increased oxidized glutathione was a major determinant of the difference between the SuHx and control groups. Conclusion: Our data suggests that decreased RV serum levels of amino acids in SuHx rats may be driven by increased consumption in the pulmonary vasculature. Given that glutamine levels in the RV are decreased, while being increased intracellularly in MVECs, we hypothesize that glutamine consumption in the lung microvasculature may be driven in part, to produce reduced glutathione. This is also supported by the oxidized glutathione gradient across the pulmonary vasculature in our experiments. These results provide the basis for a mechanistic study aimed at understanding how interrupting glutathione and/or branched-chain amino acid metabolism in MVECs contributes to PAH. NHLBI grant K08HL145132 (J.S.), NHLBI grant R01HL148112 01 (L.S), NHLBI grant R01HL151530 (K.S) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Causal associations between serum amino acid levels and osteoarthritis: a Mendelian randomization study

The association between serum amino acid (AA) levels and osteoarthritis (OA) risk remains unclear. We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effects of. serum AA levels on the OA risk by using summary-level genome-wide association study (GWAS) data. Inverse variance weighted (IVW) and Wald ratio were used as the main analysis.We also applied MR-Egger, Weighted median and Robust Adjusted Profile Score (MR.RAPS) methods. Heterogeneity and horizontally pleiotropic outliers were checked. The causal effects of AAs on early-onset all OA were explored. We also performed multivariable MR (MVMR) and conducted the bidirectional MR. The results suggested that genetically predicted alanine (Ala), tyrosine (Tyr) and isoleucine (Ile) levels were significantly associated with OA risk (e.g., association between Ala and hip/knee OA risk: OR = 0.82, 95% CI = 0.75 ∼ 0.90, p = 1.54E-05). The study yielded little evidence of associations between genetically predicted AA levels with early-onset all OA risk. When adjusting the BMI in the MVMR model, suggestive causal effects of Ala and Tyr were also identified, while the effects of Ile substantially attenuated with OA risk. No significant associations between OA and AA levels were observed after testing for bidirectionality. Some AAs, such as Ala, Tyr and Ile likely affects the OA risk especially at hip or knee joints. The findings highlight the important role that serum AAs might play in the development of OA and provided new treatment approaches to OA.

Dietary Intake and Circulating Amino Acid Concentrations in Relation with Bone Metabolism Markers in Children Following Vegetarian and Omnivorous Diets.

Scientific studies reported that most vegetarians meet the total protein requirements; however, little is known about their amino acid intakes. We aimed to assess dietary intake and serum amino acid levels in relation to bone metabolism markers in prepubertal children on vegetarian and traditional diets. Data from 51 vegetarian and 25 omnivorous children aged 4-9 years were analyzed. Dietary intake of macro- and micronutrients were assessed using the nutritional program Dieta 5®. Serum amino acid analysis was performed using high-pressure liquid chromatography technique, 25-hydroxyvitamin D and parathormone-electrochemiluminescent immunoassay, and bone metabolism markers, albumin, and prealbumin levels using enzyme-linked immunosorbent assay. Vegetarian children had a significantly lower intake of protein and amino acids with median differences of about 30-50% compared to omnivores. Concentrations of four amino acids (valine, lysine, leucine, isoleucine) in serum varied significantly by diet groups and were lower by 10-15% in vegetarians than meat-eaters. Vegetarian children also had lower (p < 0.001) serum albumin levels compared to omnivores. Among bone markers, they had higher (p < 0.05) levels of C-terminal telopeptide of collagen type I (CTX-I) than omnivores. Correlation patterns between amino acids and bone metabolism markers differed in the vegetarian and omnivore groups. Out of bone markers, especially osteoprotegerin was positively correlated with several amino acids, such as tryptophan, alanine, aspartate, glutamine, and serine, and ornithine in vegetarians. Vegetarian children consumed apparently sufficient but lower protein and amino acids compared to omnivores. In circulation these differences were less marked than in the diet. Significantly lower amino acid intake and serum levels of valine, lysine, leucine, and isoleucine as well as the observed correlations between serum amino acids and biochemical bone marker levels indicated the relations between diet, protein quality, and bone metabolism.