Concentrations Of Serine Research Articles

Comparative Study on Growth and Metabolomic Profiles of Six Lactobacilli Strains by Sodium Selenite

Selenium (Se) has garnered increasing attention in the field of nutrition, as it is essential for both humans and animals. Certain microorganisms can enrich inorganic selenium and convert it into organic selenium. The growth and metabolomic profiles of six lactobacilli strains exposed to 50 μg/mL of sodium selenite were performed using gas chromatography tandem time-off light mass spectrometry (GC-TOF-MS) analysis. The addition of selenium significantly increased both the population and weight of the Lacticaseibacillus rhamnosus PS5, Lbs. rhamnosus RT-B, Limosilactobacillus reuteri 3630, and Lmb. reuteri 1663 strains, while those of the other two strains decreased. A total of 271 metabolites were determined, with their concentrations ranked from highest to lowest as follows: organic acids and derivatives, oxygen compounds, lipids and lipid-like molecules, and benzenoids. In certain groups, the concentrations of serine, aspartic acid, trehalose, palmitic acid, methylthreonine, and melibiose increased significantly, whereas glucuronic acid, ribose, ornithine, and methionine were downregulated. The metabolic pathways were significantly associated with ABC transporters, glycine, serine, threonine metabolism, and aminobenzoate degradation and other pathways. Based on these findings, we concluded that the transport, absorption, assimilation, and stress response to selenium by lactobacilli in metabolomic changed. Furthermore, the metabolomic alterations among different types of lactobacilli varied primarily due to their distinct properties.

The Effects of L-citrulline Supplementation on the Athletic Performance, Physiological and Biochemical Parameters, Antioxidant Capacity, and Blood Amino Acid and Polyamine Levels in Speed-Racing Yili Horses.

The objective of this study was to evaluate the effects of pre-exercise L-citrulline supplementation on the athletic performance of Yili speed-racing horses during a high-intensity exercise. On the 20th day of the experiment, blood samples were collected at 3 h and 6 h post-supplementation to measure the amino acid and polyamine concentrations. On the 38th day of the experiment, the horses participated in a 2000 m speed race, and three distinct blood samples were gathered for assessing blood gases, hematological parameters, the plasma biochemistry, antioxidant parameters, and NO concentrations. The results indicate that the L-citrulline group showed a significant increase in the plasma citrulline and arginine concentrations. Conversely, the concentrations of alanine, serine, and threonine were significantly decreased. The glycine concentration decreased significantly, while there was a trend towards an increase in the glutamine concentration. Additionally, the levels of putrescine and spermidine in the plasma of the L-citrulline group were significantly increased. In terms of exercise performance, L-citrulline can improve the exercise performance of sport horses, significantly reduce the immediate post-race lactate levels in Yili horses, and accelerate the recovery of blood gas levels after an exercise. Furthermore, in the L-citrulline group of Yili horses, The levels of the total protein of plasma, superoxide dismutase, catalase, and lactate dehydrogenase were significantly increased both 2 h before and 2 h after the race. The total antioxidant capacity showed a highly significant increase, while the malondialdehyde content significantly decreased. In the immediate post-race period, the creatinine content in the L-citrulline group significantly increased. In conclusion, this study demonstrates that L-citrulline supplementation can influence the circulating concentrations of L-citrulline and arginine in Yili horses, enhance the antioxidant capacity, reduce lactate levels, and improve physiological and biochemical blood parameters, thereby having a beneficial effect on the exercise performance of athletic horses.

Investigating the etiology of ocular changes in Monodactylus argenteus housed in a shoaling ring exhibit.

To evaluate the pathologic ocular changes in a population of aquarium-housed Monodactylus argenteus and investigate potential underlying causes for the large number of affected fish in this exhibit. 11 Monodactylus argenteus were evaluated from a shoaling ring exhibit within an aquarium, and 19 control fish without ocular abnormalities were obtained from commercial fish suppliers. Physical and ocular examinations were performed antemortem. Postmortem samples of liver, heart, dorsal epaxial muscle, and lenses of affected and control fish were analyzed for amino acid profiles. The aqueous humor from affected and control fish was collected postmortem, and osmolality was analyzed. Tissues from affected and control fish were submitted for histopathology. Ocular abnormalities in affected fish included corneal lesions, cataracts, lens capsule rupture, and unilateral left-sided lens luxation and buphthalmos. Lens luxation and buphthalmos were directly correlated. Aqueous humor osmolality in control fish differed significantly compared to affected fish but was not correlated to lens abnormality score. Affected fish had significantly lower lens concentrations of arginine, asparagine, glycine, isoleucine, serine, and tyrosine than control fish. One affected fish had severe buphthalmos, cataracts, and panophthalmitis caused by gram-positive cocci. Cataracts and traumatic lesions were common in affected M argenteus. Dietary amino acid content and aqueous humor osmolality imbalances were not likely a cause of the cataracts. Differences in lens amino acid concentrations between affected and control fish may be related to cataract formation. Consideration of species-appropriate tank parameters may mitigate ocular lesions including cataracts in aquarium fish.

Leucine requirement determined in healthy young adult males using the indicator amino acid oxidation method

BackgroundPrevious studies proposed varying leucine requirements for adults ranging from 25 to 40 mg⋅kg−1⋅d−1, but often these studies did not test intakes exceeding 40 mg⋅kg−1⋅d−1. Data using the indicator amino acid oxidation (IAAO) method suggest a higher requirement of 55 mg⋅kg−1⋅d−1 on the basis of the total branched-chain amino acids requirement, but not leucine independently. ObjectivesThe IAAO method was used to determine the leucine requirement in healthy young adult males. MethodsTen healthy adult males (26.9 ± 1.87 y, mean ± SEM) were studied at 7 leucine intakes; each studied over a 3-d period. Following 2-d of preadaptation to adequate protein intake (1.0 g⋅kg−1⋅d−1), subjects received experimental diets containing the randomly assigned test leucine intake (10, 20, 30, 40, 50, 65, and 75 mg⋅kg−1⋅d−1) for 8 h. The rate of the release of 13CO2 from the oxidation of L-[1-13C]phenylalanine (F13CO2) was measured on the third day, and the leucine requirement was determined using mixed-effect change-point regression and the F13CO2 data in R. The 95% confidence interval was calculated using parametric bootstrap. The effect of leucine intake on the concentration of plasma amino acids, insulin, and glucose were assessed using repeated measures analysis of variance and linear mixed effects. ResultsThe mean leucine requirement was 33.6 mg⋅kg−1⋅d−1 with a lower and upper 95% confidence of 26.16, 41.04 mg⋅kg−1⋅d−1. Higher leucine intakes were associated with increased plasma leucine, and decreased valine, isoleucine, and serine concentrations. ConclusionsThe leucine requirement of young adult males is ∼34 mg⋅kg−1⋅d−1, which aligns with previously published tracer balance experiments.This trial was registered at http://clinicaltrials.gov (https://clinicaltrials.gov/study/NCT05394155?term=leucine%20young%20adult&rank=1) as NCT05394155.

Effect of arginine, glycine + serine concentrations, and guanidinoacetic acid supplementation in vegetable-based diets for chickens

The study investigated guanidinoacetic acid (GAA) supplementation with varying dietary digestible arginine (Arg) and glycine+serine (Gly+Ser) concentrations in the starter phase, exploring respective carry-over effects on growth performance, blood chemistry, incidence of pectoral myopathies and proximate composition in broilers. A total of 2,800 one-day-old male broiler chicks were distributed in a central composite design with 2 factors and double experimental mesh, represented by supplementation or omission of 0.6 g per kg of GAA, with a central point represented by 107% of Arg and 147% of Gly+Ser, 4 factorial points (combinations of Arg/Gly+Ser concentrations: 96.4/132.5%; 117.6/132.5%; 96.4/161.5%, and 117.6/132.5%), and 4 axial points (combinations of axial points estimated for Arg and Gly+Ser, with the central points of 92/147%; 122/147%; 107/126.5, and 107/167.5%), totaling 18 treatments, 4 repetitions to factorial and axial points, 24 replicates to the central point, and 25 birds per pen. Feed conversion ratio (FCR) from d 1 to 10 had a linear response (P = 0.009) for the decreasing Arg content and a quadratic response (P = 0.047) for Gly+Ser concentrations. Broilers supplemented GAA had lower FCR compared with nonsupplemented groups from d 1 to 10 (P = 0.048) and d 1 to 42 (P = 0.026). Aspartate aminotransferase (AST) exhibited increasing and decreasing linear effects as a function of Arg (P = 0.008) and Gly+Ser (P = 0.020) concentrations, respectively. Guanidinoacetic acid decreased serum AST (P = 0.028). Guanidinoacetic acid reduced moderate + severe (P = 0.039) and mild (P = 0.015) Wooden Breast scores. The occurrence of normal White Striping increased (P = 0.002), while severe score was reduced (P = 0.029) with GAA supplementation. In conclusion, increased digestible Arg:Lys and 14% and 6% above the recommendations (107% and 147%), respectively, provided improved FCR during the starter phase. Dietary GAA supplementation (0.6 g per kg) improved FCR, reduced severity of breast myopathies and appears to have reduced muscle damage in broilers fed plant-based diets.

Association Between Serine Concentration and Coronary Heart Disease: A Case-Control Study.

Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients. This case-control study included 428 case-control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of >70% and controls with stenosis of <30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD. Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 μg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 μg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90-0.99; P = 0.010). Patients with a serine concentration of ≥13.41 μg/mL had a lower CHD risk than those with a serine concentration of <13.41 μg/mL (odds ratio [OR] 0.57, 95% CI 0.39-0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (P interaction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87-0.98; P = 0.013) than in females. This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.

Uninterrupted in vivo cerebral microdialysis measures of the acute neurochemical response to a single or repeated concussion in a rat model combining force and rotation

Altered extracellular amino acid concentrations following concussion or mild traumatic brain injury can result in delayed neuronal damage through overactivation of NMDA glutamatergic receptors. However, the consequences of repeated concussions prior to complete recovery are not well understood. In this study, we utilized in vivo cerebral microdialysis and a weight-drop model to investigate the acute neurochemical response to single and repeated concussions in adult rats that were fully conscious. A microdialysis probe was inserted into the hippocampus and remained in place during impact. Primary outcomes included concentrations of glutamate, GABA, taurine, glycine, glutamine, and serine, while secondary outcomes were righting times and excitotoxic indices. Compared to sham injury, the first concussion resulted in significant increases in glutamate, GABA, taurine, and glycine levels, longer righting times, and higher excitotoxic indices. Following the second concussion, righting times were significantly longer, suggesting cumulative effects of repeated concussion while only partial increases were observed in glutamate and taurine levels. GABA and glycine levels, and excitotoxic indices were comparable to sham injury. These findings suggest that single and repeated concussions may induce acute increases in several amino acids, while repeated concussions could exacerbate neurological symptoms despite less pronounced neurochemical changes.

Evaluation of lauric acid enhancement of black soldier fly larvae from coconut.

The current study evaluated the potential enhancement of lauric acid (LA) in black soldier fly, Hermetia illucens, (L.) (Diptera: Stratiomyidae) larvae (BSFL), a source of this short-chain fatty acid which has antimicrobial and immunostimulatory properties. Replicate groups of BSFL were reared on either the coconut or Gainesville diet for 7 days. After the rearing period, BSFL were harvested, purged, dried, and subjected to proximate, fatty acid and amino acid compositions, and pepsin digestibility analyses. Results demonstrate changes in proximate composition. BSFL reared on the coconut had significantly (P = 0.002) higher lipid content (47.3% vs. 25.2%) on a dry-matter basis. The LA concentration in BSFL produced on the coconut was 31% greater than those reared on Gainesville, resulting in almost 150% more LA. Furthermore, BSFL-fed coconut had reduced crude protein (29.7% of dry weight) and ash (3.7% of dry weight) relative to those fed Gainesville (43.4% and 7.5% for crude protein and ash, respectively) but higher pepsin digestibility (91.0% vs. 87.0%). The relative amounts of various amino acids in the 2 BSFL meals did not differ extensively, with statistically lower concentrations of only phenylalanine and tryptophan and higher concentrations of alanine, arginine, isoleucine, leucine, and serine in BSFL reared on coconut. Results demonstrate that the nutritional composition of BSFL can be manipulated, and an enhancement of LA concentrations of 150% was achieved with coconut, which has value for BSFL as a feed for various livestock, including aquaculture. Lower protein content is a tradeoff in terms of BSFL value as a feed additive.

Serine deamination by human serine racemase synergizes with antibiotics to curtail the replication of Chlamydia trachomatis

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates the anti-chlamydial effect of elevated serine concentrations. In addition to reversibly converting l-serine to d-serine, serine racemase also deaminates serine via β-elimination. We have determined that d-serine does not directly impact Chlamydia; rather, ammonia generated by serine deamination limits the productive chlamydial replication. Our findings imply that ammonia produced within host cells can traverse the chlamydial inclusion membrane. Further, this property of serine deaminase can be exploited to sensitize Chlamydia to concentrations of doxycycline that are otherwise not bactericidal. Because exogenously elevated levels of serine can be tolerated over extended periods, the broad expression pattern of serine racemase indicates it to be a host enzyme whose activity can be directed against multiple intracellular bacterial pathogens. From a therapeutic perspective, demonstrating host metabolism can be skewed to generate an anti-bacterial metabolite that synergizes with antibiotics, we believe our results provide a new approach to target intracellular pathogens.

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis.

Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause-effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

Amino acid distribution in blood following high-intensity interval exercise: a preliminary study.

This study investigated the effect of high-intensity interval exercise on total and individual amino acid concentrations in red blood cells (RBCs) and plasma. Seven males (31 ± 13yr) provided venous blood samples at rest, immediately and 15min and 30min following an 8-min high-intensity exercise bout. The exercise bout was 16 × 15s cycle efforts at 0.4N/kg of body mass and 90rpm, interspersed with 15s passive recovery. Total and individual amino acid concentrations of RBC and plasma and blood cell parameters were analysed. No significant differences for total amino acid concentrations between RBC and plasma were found. Individual amino acid analyses showed significant interaction effects for alanine and α-aminoadipic acid (P < 0.05), with plasma alanine significantly increased from baseline across the recovery period (P < 0.001). Blood fraction (group) effects showed greater concentrations of glycine, serine, asparagine, aspartic acid, glutamic acid, α-aminoadipic acid and ornithine in RBC, while greater concentrations of alanine, α-aminobutyric acid, valine, leucine, isoleucine, threonine, proline, phenylalanine, glutamine, tryptophan and cystine were found in plasma (P < 0.05). Comparable levels of histidine, lysine and tyrosine were observed between blood fractions. Significant differences in the variation of total amino acids in RBC were reported with higher variance at rest compared to following exercise (P = 0.01). Haemoglobin, pack cell volume and white blood cell count significantly increased immediately following exercise (P < 0.05) but returned to baseline after 15min recovery. These results support the notion of individualised amino acid transportation roles for RBC and plasma during exercise.

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed. We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC). Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores. Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Metabolomics of Cerebrospinal Fluid Amino and Fatty Acids in Early Stages of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative autoimmune disease of the central nervous system (CNS) damaging myelin and axons. Diagnosis is based on the combination of clinical findings, magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid (CSF). Metabolomics is a systematic study that allows us to track amounts of different metabolites in a chosen medium. The aim of this study was to establish metabolomic differences between the cerebrospinal fluid of patients in the early stages of multiple sclerosis and healthy controls, which could potentially serve as markers for predicting disease activity. We collected CSF from 40 patients after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS, and the CSF of 33 controls. Analyses of CSF samples were performed by using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector. Significant changes in concentrations of arginine, histidine, spermidine, glutamate, choline, tyrosine, serine, oleic acid, stearic acid and linoleic acid were observed. More prominently, Expanded Disability Status Scale values significantly correlated with lower concentrations of histidine. We conclude that these metabolites could potentially play a role as a biomarker of disease activity and predict presumable inflammatory changes.

Changes in free amino acid profile in goats with pregnancy toxemia.

Pregnancy toxemia is a metabolic disorder that afflicts goats when the heightened energy requirements preceding parturition are not sufficiently satisfied. At present, the potential association between pregnancy toxemia and the free amino acid composition in hair goats remains uncharted territory. The purpose of this study is to investigate the free amino acid profile in goats during the pivotal three weeks preceding delivery, distinguishing among those with subclinical pregnancy toxemia (SPT), clinical pregnancy toxemia (CPT), and those in the control group (CG). Additionally, the study aims to investigate any potential relationship between the amino acid profile and beta hydroxy butyric acid (BHBA) levels. The researchers analyzed a total of 50 goats, comprising 20 goats with SPT, 20 with CPT, and 10 in the CG. The serum free amino acid profile was determined using a gas chromatography flame ionization detector (GC-FID) device. BHBA concentration in goats with CPT and SPT was significantly higher than KG (p < 0.001). Furthermore, in goats with CPT, the glucose concentration was significantly lower than in CG (p < 0.012). In goats with CPT and SPT, the concentration of valine, one of the gluconeogenic amino acids, was significantly higher than in control group (p < 0.001), while histidine concentration was significantly lower (p < 0.020) than in control group. Specifically in goats with CPT, the concentrations of alanine (p < 0.002), serine (p < 0.001), and threonine (p < 0.043) were significantly lower than in control group. Moreover, the concentration of phenylalanine, which is both a glycogenic and ketogenic amino acid, was significantly lower (p < 0.028) in goats with SPT compared to the control group. The Fisher ratio (p < 0.010) and Glycine/Alanine ratio (p < 0.001) were significantly higher inpregnancy toxemia goats with than in control group goats, indicating a poor nutritional and energy status of the goats during the prepartum period. In summation, the findings of this study underscore that amino acids exhibiting marked concentration variations hold considerable promise in the diagnosis, prognosis, and therapeutic management of pregnancy toxemia.

Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease.

Hyperglucagonaemia contributes to the pathophysiology in type 2 diabetes (T2D), but the mechanisms behind the inappropriate glucagon secretion are not fully understood. Glucagon and amino acids are regulated in a feedback loop referred to as the liver-α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver-α cell axis resulting in hyperglucagonaemia and hyperaminoacidaemia. We investigated the associations between circulating glucagon, amino acids, and liver fat content in a cohort of individuals with T2D. We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses. Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). The positive association between plasma glucagon concentrations and liver fat content was confirmed in the multivariable regression analyses. Plasma concentrations of isoleucine and glutamate were increased, and glycine and serine concentrations were decreased in individuals with NAFLD. Concentrations of other amino acids were similar between individuals with and without NAFLD, and no clear association was seen between liver fat content and amino acids in the regression analyses. MRS-diagnosed NAFLD in T2D is associated with hyperglucagonaemia and elevated plasma concentrations of isoleucine and glutamate and low plasma concentrations of glycine and serine. Whether NAFLD and glucagon resistance per se induce these changes remains to be elucidated.

Longitudinal anatomical and visual outcome of macular telangiectasia type 2 in Asian patients

Limited information regarding the anatomical and visual prognosis of macular telangiectasia (MacTel) type 2 in the Asian population is currently available. Herein, we conducted a retrospective longitudinal analysis of Japanese patients diagnosed with MacTel type 2. Disease progression was evaluated using the Simple MacTel Classification developed by Chew EY et al. in 2023, and its association with visual changes was analyzed. Sixteen eyes of eight Japanese patients were included in the study, with an average follow-up period of 8.2 ± 3.9 years (range, 2.2–14.0). At the initial visit, 7 (44%) and 5 (31%) eyes were classified as Grade 2 (central ellipsoid zone break) and Grade 3 (noncentral pigment), respectively. The proportion of eyes that progressed by 1 or 2-steps in grade after 1, 3, 5, 8, and 12 years was 0%, 14%, 43%, 70%, and 100%, or 0%, 7%, 7%, 30%, and 75%, respectively. The visual acuity significantly deteriorated during the follow-up period, particularly in the two eyes with full-thickness macular holes (FTMH). Three out of 7 patients exhibited low serum serine concentrations, although no apparent correlation with anatomical or visual outcomes was observed. Overall, this cohort demonstrated chronic disease progression, both anatomically and functionally, in eyes with MacTel type 2, with FTMH potentially associated with greater visual loss.

Inulin Supplementation Modulates the Hepatic Transcriptome, Metabolome, and Ferritin Content in Ovariectomized Rats.

Liver is an important metabolic organ regulating whole-body homeostasis. This study aims to investigate how prebiotic-induced changes in the metabolic activity of the gut microbiome (GM) and dietary calcium depletion modulates the hepatic metabolome and transcriptome. The serum metabolome, liver metabolome, and transcriptome are determined on samples from ovariectomized (OVX) rats fed a control diet (Control, n = 7), a control diet supplemented with 5% w/w inulin (Inulin, n = 7), or a calcium-deficient diet (CaDef, n = 7). Inulin fortification is associated with higher serum concentrations of acetate, 3-hydroxybutyrate, and reduced concentration of dimethyl sulfone, revealing that changes in the metabolic activity of the GM are reflected in circulating metabolites. Metabolomics also reveal that the inulin-fortified diet results in lower concentrations of hepatic glutamate, serine, and hypoxanthine while transcriptomics reveal accompanying effects on the hepatic expression of ferric iron binding-related genes. Inulin fortification also induces effects on the hepatic expression of genes involved in olfactory transduction, suggesting that prebiotics regulate liver function through yet unidentified mechanisms involving olfactory receptors. Inulin ingestion impacts hepatic gene expression and is associated with an upregulation of ferritin synthesis-related genes and liver ferritin content.

Intermediate metabolites and molecular correlates of one‑carbon and nutrient metabolism differ in tissues from Holstein fetuses

Methionine and folate cycles along with transsulfuration comprise the one‑carbon metabolism (OCM) pathway. Amino acids and other nutrients feed into OCM, which is central to cellular function. mRNA abundance, proteins (Western blotting), and metabolites (GC-MC) associated with OCM were used to characterize these mechanisms in fetal tissues. Liver, whole intestine, and semitendinosus muscle were harvested from fetuses in 6 multiparous Holstein cows (37 kg milk/d, 100 d gestation). Data were analyzed using PROC MIXED (SAS 9.4). Protein abundance of BHMT was greatest (P < 0.01) in liver suggesting active remethylation of homocysteine to methionine. This idea was supported by the greater (P < 0.05) mRNA of CBS, BHMT, MTR, SHMT1, and MAT1A (encoding OCM enzymes) in liver. The antioxidant protein GPX3 had greatest (P < 0.05) abundance in liver, whereas the glutathione-transferase GSTM1 was 5-fold greater (P < 0.05) in intestine than liver and muscle. Greatest concentrations of glycine, serine, and taurine along with lower cysteine underscored the relevance of OCM in fetal liver. Phosphoethanolamine concentration was greatest (4-fold, P < 0.05) in intestine and along with the greatest (P < 0.05) mRNA of SLC44A1 (choline transporter), CHKA, and CEPT1 underscored the importance of the CDP-choline pathway. Greatest (P < 0.05) mRNA of PPARA, CPT1A, and HMGCS2 along with lower PCK1 in liver highlighted a potential reliance on fatty acid oxidation. In contrast, greater (P < 0.05) concentration of myo-inositol in muscle and intestine suggested both tissues rely on glucose as main source of energy. Future research should address how environmental inputs such as maternal nutrition alter these pathways in fetal tissues and their phenotypic outcomes.

Possible-sarcopenic screening with disturbed plasma amino acid profile in the elderly

BackgroundThe mass and strength of skeletal muscle decline with age, leading to its progressive dysfunction. High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and the identification of biomarkers. However, the role of amino acid metabolism in possible sarcopenia remains unclear.ObjectivesThe aim of this study included exploring variations in plasma amino acid concentrations in elderly individuals who have possible sarcopenia and further attempting to characterize a distinctive plasma amino acid profile through targeted metabolomics.MethodsA cross-sectional, correlational research design was used for this study. Thirty possible-sarcopenic elderly participants were recruited (n = 30), as determined by the Asian Working Group for Sarcopenia (AWGS). Meanwhile, a reference group of non-sarcopenic (sex-, age-, and Appendicular Skeletal muscle Mass Index (ASMI)-matched non-sarcopenic controls, n = 36) individuals was included to compare the potential differences in metabolic fingerprint of the plasma amino acids associated with sarcopenia. Both groups were conducted the body composition analysis, physical function examination, and plasma amino acid-targeted metabolomics. The amino acids in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS–MS). Also, orthogonal partial least-squares-discriminant analysis (OPLS-DA) was applied to characterize the plasma amino acid profile.ResultsWith respect to Handgrip Strength (HGS), the Five-Repetition Chair Stand Test (CS-5), the Six-Minute Walking Test (6MWT), the arm curl, the 30 s-Chair Stand Test (CST), the 2-Minute Step Test (2MST), the Timed Up-and-Go Test (TUGT), there was a decline in skeletal muscle function in the possible-sarcopenic group compared to the non-sarcopenic group. The mean plasma concentrations of arginine, asparagine, phenylalanine, serine, lysine, glutamine, and threonine were significantly lower in the possible sarcopenia group, whereas cirulline, proline, serine, and glutamic acid concentrations were higher. According to the multi-analysis, glutamine, serine, lysine, threonine, and proline were determined as the potential markers that indicated possible sarcopenia.ConclusionsThe findings characterize significantly altered plasma amino acid metabolisms in the elderly with possible sarcopenia, which aids to screening people who are at a high risk of developing condition, and motivating to design new preventive and therapeutic approaches.

Blockade of glucagon increases muscle mass and alters fiber type composition in mice deficient in proglucagon-derived peptides.

Glucagon is secreted from pancreatic α-cells and plays an important role in amino acid metabolism in liver. Various animal models deficient in glucagon action show hyper-amino acidemia and α-cell hyperplasia, indicating that glucagon contributes to feedback regulation between the liver and the α-cells. In addition, both insulin and various amino acids, including branched-chain amino acids and alanine, participate in protein synthesis in skeletal muscle. However, the effect of hyperaminoacidemia on skeletal muscle has not been investigated. In the present study, we examined the effect of blockade of glucagon action on skeletal muscle using mice deficient in proglucagon-derived peptides (GCGKO mice). Muscles isolated from GCGKO and control mice were analyzed for their morphology, gene expression and metabolites. GCGKO mice showed muscle fiber hypertrophy, and a decreased ratio of type IIA and an increased ratio of type IIB fibers in the tibialis anterior. The expression levels of myosin heavy chain (Myh) 7, 2, 1 and myoglobin messenger ribonucleic acid were significantly lower in GCGKO mice than those in control mice in the tibialis anterior. GCGKO mice showed a significantly higher concentration of arginine, asparagine, serine and threonine in the quadriceps femoris muscles, and also alanine, aspartic acid, cysteine, glutamine, glycine and lysine, as well as four amino acids in gastrocnemius muscles. These results show that hyperaminoacidemia induced by blockade of glucagon action in mice increases skeletal muscle weight and stimulates slow-to-fast transition in type II fibers of skeletal muscle, mimicking the phenotype of a high-protein diet.