Maternal separation regulates sensitivity of stress-induced depression in mice by affecting hippocampal metabolism.

Depression is a serious mental illness. Previous studies found that early life stress (ELS) plays a vital role in the onset and progression of depression. However, relevant studies have not yet been able to explain the specific effects of early stress on stress-induced depression sensitivity and individual behavior during growth. Therefore, we constructed a maternal separation (MS) model and administered chronic social frustration stress at different stages of their growth while conducting metabolomics analysis on the hippocampus of mice. Our results showed that the immobility time of mice in the forced swimming test was significantly reduced at the end of MS. Meanwhile, mice with MS experience significantly decreased total movement distance in the open field test and sucrose preference ratio in the sucrose preference test when subjected to chronic social defeat stress (CSDS) during adolescence. In adulthood, the results were the opposite. In addition, we found that level changes in metabolites such as Beta-alanine, l-aspartic acid, 2-aminoadipic acid, and Glycine are closely related to behavioral changes. These metabolites are mainly enriched in Pantothenate, CoA biosynthesis, and Beta Alanine metabolism pathways. Our experiment revealed that the effects of ELS vary across different age groups. It will increase an individual's sensitivity to depression when facing CSDS in adolescence, but it will reduce their sensitivity to depression when facing CSDS in adulthood. This may be achieved by regulating the hippocampus's Pantothenate and CoA biosynthesis and Beta Alanine metabolism pathways represented by Beta-alanine, l-Aspartic acid, 2-aminoadipic acid, and Glycine metabolites.

A Comparative Biochemical Study Between L-Carnosine and ß-Alanine in Amelioration of Hypobaric Hypoxia-Induced Skeletal Muscle Protein Loss.

Rathor, Richa, Sukanya Srivastava, and Geetha Suryakumar. A comparative biochemical study between L-carnosine and ß-alanine in amelioration of hypobaric hypoxia-induced skeletal muscle protein loss. High Alt Med Biol. 24:302-311, 2023. Background: Carnosine (CAR; ß-alanyl-L-histidine), a biologically active dipeptide is known for its unique pH-buffering capacity, metal chelating activity, and antioxidant and antiglycation property. ß-Alanine (ALA) is a nonessential amino acid and used to enhance performance and cognitive functions. Hypobaric hypoxia (HH)-induced muscle protein loss is regulated by multifaceted signaling pathways. The present study investigated the beneficial effects of CAR and ALA against HH-associated muscle loss. Methodology: Simulated HH exposure was performed in an animal decompression chamber. Gastric oral administration of CAR (50 mg·kg-1) and ALA (450 mg·kg-1) were given daily for 3 days and at the end of the treatment, hindlimb skeletal muscle tissue was excised for western blot and biochemical assays. Results: Cosupplementation of CAR and ALA alone was able to ameliorate the hypoxia-induced inflammation, oxidative stress (FOXO), ER stress (GRP-78), and atrophic signaling (MuRF-1) in the skeletal muscles. Creatinine phospho kinase activity and apoptosis were also decreased in CAR- and ALA-supplemented rats. However, CAR showed enhanced protection in HH-induced muscle loss as CAR supplementation was able to enhance protein concentration, body weight, and decreased the protein oxidation and ALA administration was not able to restore the same. Conclusions: Hence, the present comprehensive study supports the fact that CAR (50 mg·kg-1) is more beneficial as compared with ALA (450 mg·kg-1) in ameliorating the hypoxia-induced skeletal muscle loss.

Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting.

BACKGROUND: Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH]i ) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesized by the enzyme carnosine synthase (CARNS), remove lipid peroxidation-derived aldehydes, and buffer [pH]i . Nevertheless, their role in muscle wasting has not been studied. METHODS: Histidyl dipeptides in the rectus abdominis (RA) muscle and red blood cells (RBCs) of male and female controls (n = 37), weight stable (WS: n = 35), and weight losing (WL; n = 30) upper gastrointestinal cancer (UGIC) patients, were profiled by LC-MS/MS. Expression of enzymes and amino acid transporters, involved in carnosine homeostasis, was measured by Western blotting and RT-PCR. Skeletal muscle myotubes were treated with Lewis lung carcinoma conditioned medium (LLC CM), and ß-alanine to study the effects of enhancing carnosine production on muscle wasting. RESULTS: Carnosine was the predominant dipeptide present in the RA muscle. In controls, carnosine levels were higher in men (7.87 ± 1.98 nmol/mg tissue) compared with women (4.73 ± 1.26 nmol/mg tissue; P = 0.002). In men, carnosine was significantly reduced in both the WS (5.92 ± 2.04 nmol/mg tissue, P = 0.009) and WL (6.15 ± 1.90 nmol/mg tissue; P = 0.030) UGIC patients, compared with controls. In women, carnosine was decreased in the WL UGIC (3.42 ± 1.33 nmol/mg tissue; P = 0.050), compared with WS UGIC patients (4.58 ± 1.57 nmol/mg tissue), and controls (P = 0.025). Carnosine was significantly reduced in the combined WL UGIC patients (5.12 ± 2.15 nmol/mg tissue) compared with controls (6.21 ± 2.24 nmol/mg tissue; P = 0.045). Carnosine was also significantly reduced in the RBCs of WL UGIC patients (0.32 ± 0.24 pmol/mg protein), compared with controls (0.49 ± 0.31 pmol/mg protein, P = 0.037) and WS UGIC patients (0.51 ± 0.40 pmol/mg protein, P = 0.042). Depletion of carnosine diminished the aldehyde-removing ability in the muscle of WL UGIC patients. Carnosine levels were positively associated with decreases in skeletal muscle index in the WL UGIC patients. CARNS expression was decreased in the muscle of WL UGIC patients and myotubes treated with LLC-CM. Treatment with ß-alanine, a carnosine precursor, enhanced endogenous carnosine production and decreased ubiquitin-linked protein degradation in LLC-CM treated myotubes. CONCLUSIONS: Depletion of carnosine could contribute to muscle wasting in cancer patients by lowering the aldehyde quenching abilities. Synthesis of carnosine by CARNS in myotubes is particularly affected by tumour derived factors and could contribute to carnosine depletion in WL UGIC patients. Increasing carnosine in skeletal muscle may be an effective therapeutic intervention to prevent muscle wasting in cancer patients.

Carnosine and Beta-Alanine Supplementation in Human Medicine: Narrative Review and Critical Assessment.

The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite N-acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of Helicobacter pylori eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.

Effects of acute beta-alanine supplementation on post-exertion rating of per-ceived exertion, heart rate, blood lactate, and physical performance on the 6-minute race test in middle-distance runners.

Introduction: Background: the use of beta-alanine (BA) to increase physical performance in the heavy-intensity domain zone (HIDZ) is widely documented. However, the effect of this amino acid on the post-exertion rating of perceived exertion (RPE), heart rate (HR), and blood lactate (BL) is still uncertain. Objectives: a) to determine the effect of acute BA supplementation on post-exertion RPE, HR, and BL in middle-distance athletes; and b) to determine the effect of acute BA supplementation on physical performance on the 6-minute race test (6-MRT). Material and methods: the study included 12 male middle-distance athletes. The de-sign was quasi-experimental, intrasubject, double-blind & crossover. It had two treat-ments (low-dose BA [30 mg·kg-1] and high-dose BA [45 mg·kg-1]) and a placebo, 72 hours apart. The effect of BA was evaluated at the end of the 6-MRT and post-exertion. The variables were RPE, HR and BL, and 6-MRT (m) distance. The statistical analysis included a repeated-measures ANOVA (p < 0.05). Results: the analysis evidenced no significant differences at the end of 6-MRT for all variables (p ˃ 0.05). However, both doses of BA generated a lower post-exertion RPE. The high dose of BA caused significant increases in post-exertion BL (p ˂ 0.05). Conclusion: acute supplementation with BA generated a lower post-exertion RPE. This decrease in RPE and the post-exertion BL increase could be related to an increase in physical performance in HIDZ.

Introducción: Introducción: el uso de beta-alanina (BA) para aumentar el rendimiento físico en zo-nas con dominio de alta intensidad (HIDZ) está ampliamente documentado. Sin em-bargo, el efecto de este aminoácido sobre el índice de esfuerzo percibido (RPE), la frecuencia cardíaca (HR) y el lactato sanguíneo (BL) aún es incierto. Objetivos: a) determinar el efecto de la suplementación aguda de BA sobre el RPE, la HR y el BL posesfuerzo; y b) además del rendimiento en la prueba de carrera de 6 mi-nutos (6-MRT), en atletas de media distancia. Material y métodos: el estudio incluyó a 12 atletas masculinos de media distancia. El diseño fue cuasiexperimental, intrasujeto, doble ciego y cruzado. Incluyó dos trata-mientos (BA en dosis baja [30 mg·kg-1] y BA en dosis alta [45 mg·kg-1]) y placebo, con 72 horas de diferencia. El efecto de BA se evaluó al final de los 6-MRT y posesfuerzo. Las variables fueron RPE, HR y BL, y distancia en 6-MRT (m). El análisis estadístico in-cluyó un ANOVA de medidas repetidas (p < 0,05). Resultados: el análisis no evidenció diferencias significativas al final de los 6-MRT pa-ra todas las variables (p ˃ 0,05). Sin embargo, ambas dosis de BA generaron un menor RPE posesfuerzo. La dosis alta de BA generó incrementos significativos en el BL poses-fuerzo (p ˂ 0,05). Conclusión: la suplementación aguda con BA generó un menor RPE posesfuerzo. Esta disminución del RPE y el aumento en el BL posesfuerzo podrían estar relacionados con un aumento del rendimiento físico en HIDZ.

The Effect of ß-Alanine Supplementation on Performance, Cognitive Function and Resiliency in Soldiers.

ß-alanine is a nonessential amino acid that combines with the amino acid histidine to form the intracellular dipeptide carnosine, an important intracellular buffer. Evidence has been well established on the ability of ß-alanine supplementation to enhance anaerobic skeletal muscle performance. As a result, ß-alanine has become one of the more popular supplements used by competitive athletes. These same benefits have also been reported in soldiers. Evidence accumulated over the last few years has suggested that ß-alanine can result in carnosine elevations in the brain, which appears to have broadened the potential effects that ß-alanine supplementation may have on soldier performance and health. Evidence suggests that ß-alanine supplementation can increase resilience to post-traumatic stress disorder, mild traumatic brain injury and heat stress. The evidence regarding cognitive function is inconclusive but may be more of a function of the stressor that is applied during the assessment period. The potential benefits of ß-alanine supplementation on soldier resiliency are interesting but require additional research using a human model. The purpose of this review is to provide an overview of the physiological role of ß-alanine and why this nutrient may enhance soldier performance.

Design, synthesis, and biological evaluation of some novel naphthoquinone-glycine/ß-alanine anilide derivatives as noncovalent proteasome inhibitors.

A series of novel noncovalent glycine/ß-alanine anilide derivatives possessing 2-chloronaphthoquinone structure as a pharmacophoric unit were designed, synthesized, and evaluated for their antiproliferative and antiproteasomal activities against MCF-7 cell line, in vitro. According to biological activity results, all the target compounds showed antiproliferative activity in the range of IC50  = 7.10 ± 0.10-41.08 ± 0.14 µM and most of them exhibited inhibitory efficacy with varying ratios against the three catalytic subunits (ß1, ß2, and ß5) presenting caspase-like (C-L), trypsin-like (T-L) and chymotrypsin-like (ChT-L) activities of proteasome. The antiproteasomal activity evaluations revealed that compounds preferentially inhibited the ß5 subunit compared with ß1 and ß2 subunits of the proteasome. Among the compounds, compounds 7 and 9 showed the highest antiproliferative activity with an IC50 value of 7.10 ± 0.10 and 7.43 ± 0.25 µM, respectively. Additionally, compound 7 displayed comparable potency to PI-083 lead compound in terms of ß5 antiproteasomal activity with an inhibition percentage of 34.67 at 10 µM. This compound showed an IC50 value of 32.30 ± 0.45 µM against ß5 subunit. Furthermore, molecular modeling studies of the most active compound 7 revealed key interactions with ß5 subunit. The results suggest that this class of compounds may be beneficial for the development of new potent proteasome inhibitors.

Effects of dietary ß-alanine supplementation on growth performance, meat quality, carnosine content, amino acid composition and muscular antioxidant capacity in Chinese indigenous Ningxiang pig.

ß-alanine has been demonstrated to improve carcass traits and meat quality of animals. However, no research has been found on the effects of dietary ß-alanine in the meat quality control of finishing pigs, which are among the research focus. Therefore, this study aimed to evaluate the effects of dietary ß-alanine supplementation on growth performance, meat quality, carnosine content, amino acid composition and muscular antioxidant capacity of Chinese indigenous Ningxiang pigs. The treatments contained a basal diet (control, CON) and a basal diet supplemented with 600 mg/kg ß-alanine. Each treatment group consisted of five pens, with five pigs per pen. Results showed that compared with CON, supplemental ß-alanine did not affect the final body weight, average daily gain, average daily feed intake and the feed-to-gain ratio of pigs. Dietary ß-alanine supplementation tended to increase the pH45 min (p = 0.071) while decreasing the shear force (p = 0.085) and the drip loss (p = 0.091). Moreover, it improved (p < 0.05) the activities of glutathione peroxidase and catalase and lessened (p < 0.05) malondialdehyde concentration. Added ß-alanine in diets of finishing pigs could enhance the concentrations of arginine, alanine, and glutamate (p < 0.05) in the longissimus dorsi muscle and tended to raise the levels of cysteine, glycine and anserine (p = 0.060, p = 0.098 and p = 0.091 respectively). Taken together, our results showed that dietary ß-alanine supplementation contributed to the improvement of the carcass traits, meat quality and anserine content, the amelioration of muscle antioxidant capacity and the regulation of amino acid composition in Chinese indigenous Ningxiang pigs.

Effect of ß-alanine and sodium bicarbonate co-supplementation on the body's buffering capacity and sports performance: A systematic review.

Muscle acidification is one of the main factors causing fatigue during exercise, thus compromising performance. The sport supplements beta alanine (ß-A) and sodium bicarbonate (SB) are thought to enhance the effects of the body's buffer systems by reducing H+ concentrations. The aim of this systematic review was to analyze the effects of ß-A and SB co-supplementation on the organism's buffering capacity and sport performance. The databases PubMed, Web of Science, Medline, CINAHL and SPORTDiscus were searched until November 2021 following PRISMA guidelines. Randomized controlled trials, at least single-blind, performed in athletes of any age were considered. Nine studies including a total of 221 athletes were identified for review. Athletes were supplemented with ß-A and SB while they performed exercise tests to assess physical performance and buffer capacity. Five of the nine studies indicated there was some additional improvement in buffering capacity and performance with co-supplementation, while one study concluded that the effect was comparable to the added effects of the individual supplements. According to the results of the studies reviewed, we would recommend ß-A and SB co-supplementation during high intensity exercises lasting between 30 s and 10 min.

Regulation of Skeletal Muscle Function by Amino Acids, Especially Non-Proteinogenic Amino Acids.

Amino acids are compounds that contain an amino group (-NH2) and a carboxyl group (-COOH) and are components of proteins and materials for various bioactive molecules. The skeletal muscle, which is the largest organ in the human body, representing ~40% of the total body weight, plays important roles in exercise, energy expenditure, and glucose/amino acid usage-processes that are modulated by various amino acids and their metabolites. In this review, we address the metabolism and function of amino acids, especially non-proteinogenic amino acids, in the skeletal muscle. Leucine, a BCAA, and its metabolite, ß-hydroxy-ß-methylbutyrate (HMB), both activate mammalian target of rapamycin complex 1 (mTORC1) and increase protein synthesis, but the mechanisms of activation appear to be different. The metabolite of valine (another BCAA), ß-aminoisobutyric acid (BAIBA), is increased by exercise, is secreted by the skeletal muscle, and acts on other tissues, such as white adipose tissue, to increase energy expenditure. In addition, several amino acid-related molecules reportedly activate skeletal muscle function. Oral 5-aminolevulinic acid (ALA) supplementation can protect against mild hyperglycemia and help prevent type 2 diabetes. ß-alanine levels are decreased in the skeletal muscles of aged mice. ß-alanine supplementation increased the physical performance and improved the executive function induced by endurance exercise in middle-aged individuals. Further studies focusing on the effects of amino acids and their metabolites on skeletal muscle function will provide data essential for the production of food supplements for older adults, athletes, and individuals with metabolic diseases.

Effects of dietary supplementation with histidine and ß-alanine on blood plasma metabolome of broiler chickens at different ages.

Histidine is an essential amino acid for broiler chickens and a precursor for the dipeptides carnosine and anserine, but little information is available about its metabolism in modern, fast-growing broilers. We used untargeted metabolomics to investigate the metabolic changes caused by the use of different standardized ileal digestible His:Lys ratios in broiler diets with and without ß-alanine supplementation. A total of 2204 broilers were randomly divided into 96 pens of 23 birds each. The pens were divided into 16 blocks, each containing one pen for all six feeding groups (total of 16 pens per group). These feeding groups were fed three different His:Lys ratios (0.44, 0.54, and 0.64, respectively) without and with a combination of 0.5% ß-alanine supplementation. Five randomly selected chickens of one single randomly selected pen per feeding group were slaughtered on day 35 or 54, blood was collected from the neck vessel, and plasma was used for untargeted metabolomic analysis. Here we show that up to 56.0% of all metabolites analyzed were altered by age, whereas only 1.8% of metabolites were affected by the His:Lys ratio in the diet, and 1.5% by ß-alanine supplementation. Two-factor analysis and metabolic pathway analysis showed no interaction between the His:Lys ratio and ß-alanine supplementation. The effect of the His:Lys ratio in the diet was limited to histidine metabolism with a greater change in formiminoglutamate concentration. Supplementation of ß-alanine showed changes in metabolites of several metabolic pathways; increased concentrations of 3-aminoisobutyrate showed the only direct relationship to ß-alanine metabolism. The supplementation of ß-alanine indicated few effects on histidine metabolism. These results suggest that the supplements used had limited effects or interactions on both His and ß-alanine metabolism. In contrast, the birds' age has the strongest influence on the metabolome.

Exogenous 5-aminolevulinic acid alleviates low-temperature injury by regulating glutathione metabolism and ß-alanine metabolism in tomato seedling roots.

Food availability represents a major worldwide concern due to climate change and population growth. Low-temperature stress (LTS) severely restricts the growth of tomato seedlings. Exogenous 5-aminolevulinic acid (ALA) can alleviate the harm of abiotic stress including LTS; however, data on its protective mechanism on tomato seedling roots, the effects of organelle structure, and the regulation of metabolic pathways under LTS are lacking. In this study, we hope to fill the above gaps by exploring the effects of exogenous ALA on morphology, mitochondrial ultrastructure, reactive oxygen species (ROS) enrichment, physiological indicators, related gene expression, and metabolic pathway in tomato seedlings root under LTS. Results showed that ALA pretreatment could increase the activity of antioxidant enzymes and the content of antioxidant substances in tomato seedlings roots under LTS to scavenge the massively accumulated ROS, thereby protecting the mitochondrial structure of roots and promoting root development under LTS. Combined transcriptomic and metabolomic analysis showed that exogenous ALA pretreatment activated the glutathione metabolism and ß-alanine metabolism of tomato seedling roots under LTS, further enhanced the scavenging ability of tomato seedling roots to ROS, and improved the low-temperature tolerance of tomato seedlings. The findings provide a new insight into the regulation of the low-temperature tolerance of tomato by exogenous ALA.

Efficacy of 12 weeks oral beta-alanine supplementation in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD. METHODS: In this double-blind, randomized, placebo (PL)-controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV1 % predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co-primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed. RESULTS: Beta-alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49-4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO2 peak: +0.5 [-0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [-1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [-179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1-quartile 3); 100 (98-100)%) and PL (98 (96-100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes. CONCLUSIONS: Beta-alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed.

Aminomethanesulfonic acid illuminates the boundary between full and partial agonists of the pentameric glycine receptor.

To clarify the determinants of agonist efficacy in pentameric ligand-gated ion channels, we examined a new compound, aminomethanesulfonic acid (AMS), a molecule intermediate in structure between glycine and taurine. Despite wide availability, to date there are no reports of AMS action on glycine receptors, perhaps because AMS is unstable at physiological pH. Here, we show that at pH 5, AMS is an efficacious agonist, eliciting in zebrafish α1 glycine receptors a maximum single-channel open probability of 0.85, much greater than that of ß-alanine (0.54) or taurine (0.12), and second only to that of glycine itself (0.96). Thermodynamic cycle analysis of the efficacy of these closely related agonists shows supra-additive interaction between changes in the length of the agonist molecule and the size of the anionic moiety. Single particle cryo-electron microscopy structures of AMS-bound glycine receptors show that the AMS-bound agonist pocket is as compact as with glycine, and three-dimensional classification demonstrates that the channel populates the open and the desensitized states, like glycine, but not the closed intermediate state associated with the weaker partial agonists, ß-alanine and taurine. Because AMS is on the cusp between full and partial agonists, it provides a new tool to help us understand agonist action in the pentameric superfamily of ligand-gated ion channels.

Effects of polystyrene microplastics acute exposure in the liver of swordtail fish (Xiphophorus helleri) revealed by LC-MS metabolomics.

As global pollution, microplastics pollution has aroused growing concerns. In our experiment, the effect of microplastics acute exposure on the liver of swordtail fish was investigated by using LC-MS metabolomics. Fishes treated with high concentration polystyrene microspheres (1 µm) for 72 h were divided into three concentration groups: (A) no microplastics, (B): 1 × 106 microspheres L-1, (C): 1 × 107 microspheres L-1. Metabolomic analysis indicated that exposure to microplastics caused alterations of metabolic profiles in swordtail fish, including 37 differential metabolites were identified in B vs. A, screened out ten significant metabolites, which involved 14 metabolic pathways. One hundred three differential metabolites were identified in C vs. A, screened out 16 significant metabolites, which involved 30 metabolic pathways. Six significant metabolites were overlapping in group B vs. A and C vs. A; they are 3-hydroxyanthranilic acid, l-histidine, citrulline, linoleic acid, pantothenate, and xanthine. In addition, four metabolic pathways are overlapping in group B vs. A and C vs. A; they are beta-alanine metabolism, biosynthesis of amino acids, linoleic acid metabolism, and aminoacyl-tRNA biosynthesis. These differential metabolites were involved in oxidative stress, immune function, energy metabolism, sugar metabolism, lipid metabolism, molecule transport, and weakened feed utilization, growth performance, nutrient metabolism, and animal growth. Furthermore, we found that the number of interfered amino acids and microplastics showed a dose-effect. In summary, great attention should be paid to the potential impact of microplastics on aquatic organisms.

Multi-target action of ß-alanine protects cerebellar tissue from ischemic damage.

Brain ischemic stroke is among the leading causes of death and long-term disability. New treatments that alleviate brain cell damage until blood supply is restored are urgently required. The emerging focus of anti-stroke strategies has been on blood-brain-barrier permeable drugs that exhibit multiple sites of action. Here, we combine single-cell electrophysiology with live-cell imaging to find that ß-Alanine (ß-Ala) protects key physiological functions of brain cells that are exposed to acute stroke-mimicking conditions in ex vivo brain preparations. ß-Ala exerts its neuroprotective action through several distinct pharmacological mechanisms, none of which alone could reproduce the neuroprotective effect. Since ß-Ala crosses the blood-brain barrier and is part of a normal human diet, we suggest that it has a strong potential for acute stroke treatment and facilitation of recovery.

Stimulation of uncoupling protein 1 expression by ß-alanine in brown adipocytes.

Carnosine, which is abundant in meat, is a dipeptide composed of ß-alanine and histidine, known to afford various health benefits. It has been suggested that carnosine can elicit an anti-obesity effect via induction and activation of brown/beige adipocytes responsible for non-shivering thermogenesis. However, the relationship between carnosine and brown/beige adipocytes has not been comprehensively elucidated. We hypothesized that ß-alanine directly modulates brown/beige adipogenesis and performed an in vitro assessment to test this hypothesis. HB2 brown preadipocytes were differentiated using insulin from day 0. Cells were treated with various concentrations of ß-alanine (12.5-100 µM) during adipogenesis (days 0-8) and differentiation (days 8-10). Then, cells were further stimulated with or without forskolin, an activator of the cAMP-dependent protein kinase pathway, on day 8 or day 10 for 4 h before harvesting. We observed that HB2 cells expressed molecules related to the transport and signal transduction of ß-alanine. Treatment with ß-alanine during brown adipogenesis dose-dependently enhanced forskolin-induced Ucp1 expression; this was not observed in differentiated brown adipocytes. Consistent with these findings, treatment with ß-alanine during days 0-8 increased phosphorylation levels of CREB in forskolin-treated HB2 cells. In addition, ß-alanine treatment during brown adipogenesis increased the expression of Pparα, known to induce brown/beige adipogenesis, in a dose-dependent manner. These findings revealed that ß-alanine could target HB2 adipogenic cells and enhance forskolin-induced Ucp1 expression during brown adipogenesis, possibly by accelerating phosphorylation and activation of CREB. Thus, ß-alanine, a carnosine-constituting amino acid, might directly act on brown adipogenic cells to stimulate energy expenditure.

Effects of beta-alanine supplementation on body composition: a GRADE-assessed systematic review and meta-analysis.

Purpose: Previous studies have suggested that beta-alanine supplementation may benefit exercise performance, but current evidence regarding its effects on body composition remains unclear. This systematic review and meta-analysis aimed to investigate the effects of beta-alanine supplementation on body composition indices. Methods: Online databases, including PubMed/Medline, Scopus, Web of Science, and Embase, were searched up to April 2021 to retrieve randomized controlled trials (RCTs), which examined the effect of beta-alanine supplementation on body composition indices. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCTs. Results: Among the initial 1413 studies that were identified from electronic databases search, 20 studies involving 492 participants were eligible. Pooled effect size from 20 studies indicated that beta-alanine supplementation has no effect on body mass (WMD: -0.15 kg; 95% CI: -0.78 to 0.47; p = 0.631, I2 = 0.0%, p = 0.998), fat mass (FM) (WMD: -0.24 kg; 95% CI: -1.16 to 0.68; p = 0.612, I2 = 0.0%, p = 0.969), body fat percentage (BFP) (WMD: -0.06%; 95% CI: -0.53 to 0.40; p = 0.782, I2 = 0.0%, p = 0.936), and fat-free mass (FFM) (WMD: 0.05 kg; 95% CI: -0.71 to 0.82; p = 0.889, I2 = 0.0%, p = 0.912). Subgroup analyses based on exercise type (resistance training [RT], endurance training [ET], and combined training [CT]), study duration (<8 and ≥8 weeks), and beta-alanine dosage (<6 and ≥6 g/d) demonstrated similar results. Certainty of evidence across outcomes ranged from low to moderate. Conclusions: This meta-analysis study suggests that beta-alanine supplementation is unlikely to improve body composition indices regardless of supplementation dosage and its combination with exercise training. No studies have examined the effect of beta-alanine combined with both diet and exercise on body composition changes as the primary variable. Therefore, future studies examining the effect of the combination of beta-alanine supplementation with a hypocaloric diet and exercise programs are warranted.

Effects of Four Weeks of Beta-Alanine Supplementation Combined with One Week of Creatine Loading on Physical and Cognitive Performance in Military Personnel.

The purpose was to investigate the effects of a 7-day creatine (Cr) loading protocol at the end of four weeks of ß-alanine supplementation (BA) on physical performance, blood lactate, cognitive performance, and resting hormonal concentrations compared to BA alone. Twenty male military personnel (age: 21.5 ± 1.5 yrs; height: 1.78 ± 0.05 m; body mass: 78.5 ± 7.0 kg; BMI: 23.7 ± 1.64 kg/m2) were recruited and randomized into two groups: BA + Cr or BA + placebo (PL). Participants in each group (n = 10 per group) were supplemented with 6.4 g/day of BA for 28 days. After the third week, the BA + Cr group participants were also supplemented with Cr (0.3 g/kg/day), while the BA + PL group ingested an isocaloric placebo for 7 days. Before and after supplementation, each participant performed a battery of physical and cognitive tests and provided a venous blood sample to determine resting testosterone, cortisol, and IGF-1. Furthermore, immediately after the last physical test, blood lactate was assessed. There was a significant improvement in physical performance and mathematical processing in the BA + Cr group over time (p < 0.05), while there was no change in the BA + PL group. Vertical jump performance and testosterone were significantly higher in the BA + Cr group compared to BA + PL. These results indicate that Cr loading during the final week of BA supplementation (28 days) enhanced muscular power and appears to be superior for muscular strength and cognitive performance compared to BA supplementation alone.