Branched-chain Amino Acids Research Articles

Diet shapes and maintains the personalized native gut microbiomes in mice.

The gut microbiome plays a critical role in human health and disease. Different dietary backgrounds play an important role in the uniqueness and diversity of the gut microbiota in different individuals, which promotes heterogeneity in disease phenotypes and treatment responses. Here, we explored how diet affects the composition and function of the native gut microbiome of model mice, based on the shotgun metagenomic and metabolomic, by analyzing the gut microbiome of C57B/6J mice in different dietary backgrounds. The gut microbiomes of mice receiving different diets consistently exhibit distinct compositions across bacterial species, strains, fungi and phages. This implies that native microbial communities cannot 'homogenize' rapidly becaise of priority effects and unchanging diets. Notably, hotspot bacteria such as Limosilactobacillus reuteri, Parabacteroides distasonis and Akkermansia muciniphila were significantly different among the groups. These species harbor diverse adaptive mutations, reflecting genomic evolutionary diversity. The functional profiles of the gut microbiota also exhibit selective differences, involving the capacity for carbohydrate, branched-chain amino acid and fatty acid synthesis, as well as virulence factors, carbohydrate-active enzymes and antibiotic resistance. Furthermore, the differences in the gut microbiota also propagate to the host's serum, where structural and specific metabolite differences were observed. Metabolites that directly impact host health, such as d-glucosamine 6-phosphate and testolic acid, also show significant differences between the different dietary groups. Our findings underscore the profound influence of different dietary the composition and functionality of the gut microbiome, offering valuable insights into optimizing health outcomes through personalized nutritional interventions. © 2024 Society of Chemical Industry.

BCAT1 Associates with DNA Repair Proteins KU70 and KU80 and Contributes to Regulate DNA Repair in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain. Here, we provide further clues on its chemo-sensitizing effect. Indeed, BCAT1 protein regulates the non-homologous end joining (c-NHEJ) DNA repair pathway by physically associating with the KU70/KU80 heterodimer. BCAT1 inhibition during active repair of DNA double-strand breaks (DSBs) led to increased KU70/KU80 acetylation and impaired c-NHEJ repair, a dramatic increase in DSBs, and ultimately cell death. Our results suggest that, in T-ALL, BCAT1 possesses non-metabolic functions that confer a drug resistance mechanism and that targeting BCAT1 activity presents a novel strategy to improve chemotherapy response in T-ALL patients.

Identifying the key role of mitochondrial respiration and lipid metabolism in regulating axillary osmidrosis through proteomics analysis.

Axillary osmidrosis (AO) affects a large number of young people in Asia, resulting from a combination of body and bacterial metabolism. This study aimed to explore the pathogenesis of AO through proteomics. Apocrine gland tissues from 3 mild and 3 severe AO patients were analyzed using 4D label-free proteomics, followed by bioinformatics analysis. The RNA and protein levels of the predicted key regulators were further validated by qPCR and immunohistochemistry in additional AO tissues. A total of 5066 proteins were identified, of which 323 were significantly upregulated and 412 were downregulated (by |log2FC|> 1 and p < 0.05). GO terms related to mitochondria, oxidation-reduction processes, and peroxisomes were significantly enriched among the upregulated DEPs, suggesting enhanced energy metabolism in severe AO patients. Downregulated DEPs were enriched in ribosome, phagosome, and platelet activation pathways according to KEGG, while upregulated DEPs were significantly enriched in metabolic pathways, valine, leucine, and isoleucine degradation, peroxisomes, and fatty acid degradation. The enriched pathways suggest that apocrine gland tissues develop AO by increasing blood flow to promote sweating and secreting excessive short-chain fatty acids by coupling mitochondrial respiration with incomplete metabolism of lipids and branched-chain amino acids. This metabolic coupling may have implications for studies on cardiovascular disease, metabolic disorders, and oxidative stress. Key proteins in the signaling network were further confirmed by qPCR and immunohistochemistry, including reduced FGA and ITGA2B, and increased EHHADH and ACOX1. Our proteomics analysis suggests a paradigm of lipid metabolism involving mitochondrial respiration and incomplete lipid and branched-chain amino acid metabolism as the pathogenesis of AO. We also suggest that EHHADH is a key regulator in promoting AO in this process.

Digging deep for nutrients and metabolites derived from high dietary protein intake and their potential functions in metabolic health.

Intake of high quantities of dietary proteins sourced from dairy, meat or plants can affect body weight and metabolic health in humans. To improve our understanding of how this may be achieved, we reviewed the data related to the availability of nutrients and metabolites in the faeces, circulation and urine. All protein sources (≥20% by energy) increased faecal levels of branched chain fatty acids and ammonia, and decreased the levels of butyrate. There were metabolites responding to dairy and meat proteins (branch chain amino acids) as well as dairy and plant proteins (p-cresol), which were increased in faecal matter. Specific to dairy protein intake, the faecal levels of acetate, indole and phenol were increased, whereas plant protein intake specifically increased the levels of kynurenine and tyramine. Meat protein intake increased the faecal levels of methionine, cysteine and alanine, and decreased the levels of propionate and acetate. The metabolite profile in the faecal matter following dairy protein intake mirrored availability in circulation or urine. These findings provide an understanding of the contrasting gut versus systemic effects of different dietary proteins, which we know to show different physiological effects. In this regard, we provide directions to determining the mechanisms for the effects of different dietary proteins.

Plasma Metabolite Profiles Between In-Center Daytime Extended-Hours and Conventional Hemodialysis.

Protein-energy wasting, characterized by disordered body protein catabolism resulting from metabolic and nutritional derangements, is associated with adverse clinical outcomes in patients undergoing hemodialysis. Extended-hours hemodialysis (≥6 h per treatment session) offers both enhanced removal of uremic solutes and better fluid management, generally allowing more liberalized dietary protein and calorie intake. This study aimed to evaluate the difference in plasma metabolite profiles among patients receiving in-center daytime extended-hours hemodialysis and those receiving conventional hemodialysis. Pre-dialysis plasma samples were obtained from 188 patients on extended-hours hemodialysis (21.9 h/week) and 286 patients on conventional hemodialysis (12.1 h/week) in Japan in 2020 using capillary electrophoresis-mass spectrometry. Group differences were compared for 117 metabolites using Wilcoxon rank-sum tests with multiple comparisons and partial least squares discriminant analysis. Additionally, propensity score-adjusted multiple regression analyses were performed to evaluate group differences for known uremic toxins, branched-chain amino acids, and lactate-to-pyruvate ratio (a possible surrogate marker of mitochondrial dysfunction). Significant differences were observed in 39 metabolites, largely consistent with the high variable importance for prediction in partial least squares discriminant analysis. Among known uremic toxins, uridine and hypoxanthine levels were significantly higher in the conventional hemodialysis group than in the extended-hours hemodialysis group, whereas trimethylamine N-oxide levels were higher in the extended-hours hemodialysis group than in the conventional hemodialysis group. Patients on extended-hours hemodialysis had higher levels of all branched-chain amino acids and a lower lactate-to-pyruvate ratio than those on conventional hemodialysis (significant difference of -8.6 [95% confidence interval, -9.8 to -7.4]). Extended-hours hemodialysis was associated with a more favorable plasma metabolic and amino acid profile; however, concentrations of most uremic toxins did not significantly differ from those of conventional hemodialysis.

Gut microbiota-mediated hsa_circ_0126925 targets BCAA metabolic enzyme BCAT2 to exacerbate colorectal cancer progression.

Recent evidence indicates that a high-fat diet (HFD) can promote tumor development, especially colorectal cancer (CRC), by influencing the microbiota. Regulatory circular RNAs (circRNAs) play an important role in modulating host-microbe interactions; however, the specific mechanisms by which circRNAs influence cancer progression by regulating these interactions remain unclear. Here, we report that consumption of a HFD modulates the microbiota by specifically upregulating the expression of the noncoding RNA hsa_circ_0126925 (herein referred to as circ_0126925) in CRC. Acting as a scaffold, circ_0126925 hinders the recruitment of the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) to branched-chain amino acid transaminase 2 (BCAT2), leading to reduced degradation of BCAT2. This reduction in targeted degradation of BCAT2 can protect tumours from limited branched-chain amino acids (BCAAs) interference by improving the metabolism of BCAAs in CRC. Taken together, these data demonstrate that circ_0126925 plays a critical role in promoting the progression of CRC by maintaining BCAA metabolism and provide insight into the functions and crosstalk of circ_0126925 in host-microbe interactions in CRC. Implications: This study preliminarily confirms that circRNAs do indeed respond to microbiota/microbial metabolites, providing further evidence for the potential development of circRNAs as diagnostic tools and/or therapeutic agents to alleviate microbiome related pathology in humans.

Development of functional foods from grouper fish-bone residues to enhance muscle strength and exercise endurance in mice

Grouper aquaculture is a key industry in Taiwan, yet its processing generates significant byproducts, leading to challenges in waste management and environmental sustainability. Recent research has focused on developing innovative methods to valorize these byproducts, with grouper bone hydrolysate (GBH) emerging as a potential candidate for applications in health promotion and exercise performance enhancement. In this study, we investigated the amino acid composition of grouper bone hydrolysate (GBH) and analyzed its peptide contents. We also investigated GBH supplementation in relation to body composition and exercise performance in mice. Male Institute of Cancer Research (ICR) mice were divided into 3 groups (n = 7 per group) and orally administered GBH once daily for 6 weeks at doses of 0 g/kg/day (vehicle), 103 mg/kg/day (GBH-1X), 205 mg/kg/day (GBH-2X), and 513 mg/kg/day (GBH-5X). The GBH was rich in branched-chain amino acids and bioactive peptides, and supplementation enhanced the exercise performance of the mice. GBH supplementation increased their exhaustive swimming time, forelimb grip strength, and tissue glycogen content while reducing fatigue markers such as lactate, ammonia, and creatine kinase. The results indicate that GBH contains dipeptides such as Leu-Ala, Glu-Asp., Met-Leu, Met-Ile, Phe-Pro, Trp-Asp., Leu- Val, and Leu-Cys, as well as tetrapeptides such as Pro-Ser-Met-Ala, Ser-Val-Pro- Ile, and Ala-Val-Pro-Trp. GBH supplementation could aid in overcoming fatigue during endurance exercise and decrease metabolic waste after acute exercise.

Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice.

The metabolism of branched-chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched-chain amino acids (BCAAs). Three metabolites of BCAAsisovalerate, 2-methylbutyrate, and isobutyrate were used to treat D-gal induced aging mice. The results showed that these treatments could delay aging in mice by providing health benefits in reducing oxidative stress and inflammation, improving muscle capacity, reversing brain acetylcholine levels, and regulating blood glucose. The mechanism was preliminarily explored by combining the gut microbiota metagenome and faecal serum metabolome. Parabacteroides merdae altered the species composition and structure of the gut microbiota in mice. Increasing the abundance of beneficial bacteria, such as Bifidobacterium pseudolongum. Three metabolites affects the gut microbiota and the body's pathways of protein and improves the overall health through a variety of signaling pathways. Overall, regulating the gut microbiota involved in branched-chain amino acid metabolism to bring health benefits may be a new way of reversing aging.

Disentangling the consequences of type 2 diabetes on targeted metabolite profiles using causal inference and interaction QTL analyses.

Circulating metabolite levels have been associated with type 2 diabetes (T2D), but the extent to which T2D affects metabolite levels and their genetic regulation remains to be elucidated. In this study, we investigate the interplay between genetics, metabolomics, and T2D risk in the UK Biobank dataset using the Nightingale panel composed of 249 metabolites, 92% of which correspond to lipids (HDL, IDL, LDL, VLDL) and lipoproteins. By integrating these data with large-scale T2D GWAS from the DIAMANTE meta-analysis through Mendelian randomization analyses, we find 79 metabolites with a causal association to T2D, all spanning lipid-related classes except for Glucose and Tyrosine. Twice as many metabolites are causally affected by T2D liability, spanning almost all tested classes, including branched-chain amino acids. Secondly, using an interaction quantitative trait locus (QTL) analysis, we describe four metabolites consistently replicated in an independent dataset from the Estonian Biobank, for which genetic loci in two different genomic regions show attenuated regulation in T2D cases compared to controls. The significant variants from the interaction QTL analysis are significant QTLs for the corresponding metabolites in the general population but are not associated with T2D risk, pointing towards consequences of T2D on the genetic regulation of metabolite levels. Finally, through differential level analyses, we find 165 metabolites associated with microvascular, macrovascular, or both types of T2D complications, with only a few discriminating between complication classes. Of the 165 metabolites, 40 are not causally linked to T2D in either direction, suggesting biological mechanisms specific to the occurrence of complications. Overall, this work provides a map of the consequences of T2D on Nightingale targeted metabolite levels and on their genetic regulation, enabling a better understanding of the T2D trajectory leading to complications.

Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.

Diabetic cardiomyopathy (DbCM), a complex metabolic disease, greatly threatens human health due to therapeutic limitations. Multi-omics approaches facilitate the elucidation of its intrinsic pathological changes. Metabolomics, RNA-seq, proteomics, and assay of transposase-accessible chromatin (ATAC-seq) were utilized to elucidate multidimensional molecular alterations in DbCM. In the heart and plasma of mice with DbCM, metabolomic analysis demonstrated significant differences in branched-chain amino acids (BCAAs) and lipids. Subsequent RNA-seq and proteomics showed that the key genes, including BCKDHB, PPM1K, Cpt1b, Fabp4, Acadm, Acadl, Acadvl, HADH, HADHA, HADHB, Eci1, Eci2, PDK4, and HMGCS2, were aberrantly regulated, contributing to the disorder of BCAAs and fatty acids. ATAC-seq analysis underscored the pivotal role of epigenetic regulation by revealing dynamic shifts in chromatin accessibility and a robust positive correlation with gene expression patterns in diabetic cardiomyopathy mice. Furthermore, motif analysis identified that KLF15 as a critical transcription factor in DbCM, regulating the core genes implicated with BCAAs metabolism. Our research delved into the metabolic alterations and epigenetic landscape and revealed that KLF15 may be a promising candidate for therapeutic intervention in DbCM.

Striatal and peripheral dopaminergic alterations related to cognitive impairment in patients with schizophrenia

Abstract Background Cognitive impairment, a major determinant of poor functioning in schizophrenia, had limited responses to existing antipsychotic drugs. The limited efficacy could be due to regional differences in the dysregulation of the dopamine system. This study investigated striatal and peripheral dopaminergic makers in schizophrenia and their relationship with cognitive impairment. Methods Thirty-three patients with schizophrenia and 36 age- and sex-matched healthy controls (HC) participated. We evaluated their cognitive performance, examined the availability of striatal dopamine transporter (DAT) using single-photon emission computed tomography with 99mTc-TRODAT, and measured plasma levels of dopaminergic precursors (phenylalanine and tyrosine) and three branched-chain amino acids (BCAA) that compete with precursors for brain uptake via ultra-performance liquid chromatography. Results Schizophrenia patients exhibited lower cognitive performance, decreased striatal DAT availability, and reduced levels of phenylalanine, tyrosine, leucine, and isoleucine, and the ratio of phenylalanine plus tyrosine to BCAA. Within the patient group, lower DAT availability in the left caudate nucleus (CN) or putamen was positively associated with attention deficits. Meanwhile, lower tyrosine levels and the ratio of phenylalanine plus tyrosine to BCAA were positively related to executive dysfunction. Among all participants, DAT availability in the right CN or putamen was positively related to memory function, and plasma phenylalanine level was positively associated with executive function. Conclusions This study supports the role of dopamine system abnormalities in cognitive impairment in schizophrenia. The distinct associations between different dopaminergic alterations and specific cognitive domain impairments suggest the potential need for multifaceted treatment approaches to target these impairments.

Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism

BackgroundA large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.MethodsBy applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.ResultsUsing gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D. Differential expression levels of one or more predicted target relevant miRNA(s) were identified for approximately 35% of the dysregulated GSEA pathways. These include miRNAs with a significant overrepresentation of targets involved in GLUT4 translocation (miR-4643 and miR-548z), signaling by receptor tyrosine kinases pathways (miR-607), and muscle contraction (miR-4658). Acquired DNA methylation changes in skeletal muscle were quantitatively small in twins with T2D compared with the co-twins without T2D. Key methylation and expression results were validated in muscle, myotubes, and/or myoblasts from unrelated subjects with T2D and controls. Finally, mimicking T2D-associated changes by overexpressing miR-548 and miR-607 in cultured myotubes decreased expression of target genes, GLUT4 and FGFR4, respectively, and impaired insulin-stimulated phosphorylation of Akt (Ser473) and TBC1D4.ConclusionsTogether, we show that T2D is associated with non- and epigenetically determined differential transcriptional regulation of pathways regulating skeletal muscle metabolism and contraction.

Effect of menopause on circulating amino acid concentrations in women with fibromyalgia and healthy women.

Fibromyalgia is a complex syndrome that appears more frequently during menopause. No previous studies have investigated the effect of menopause on amino acids in women with fibromyalgia. Therefore, we have examined serum amino acid concentrations in premenopausal and postmenopausal women with fibromyalgia and healthy women. A case-control study was carried out in 28 premenopausal and 46 postmenopausal healthy women and in 16 premenopausal and 52 postmenopausal women with fibromyalgia. This study adheres to STROBE guidelines. Amino acid content was assayed using high-performance liquid chromatography. Significant differences were found in concentrations of several amino acids (aspartic acid, glutamic acid, histidine, glycine, alanine, leucine, and taurine) between healthy premenopausal women and premenopausal women with fibromyalgia and between healthy postmenopausal women and postmenopausal women with fibromyalgia. Concentrations of other amino acids (aminoadipic acid, asparagine, threonine, arginine, 5-methyl-histidine, valine, methionine, isoleucine, phenylalanine, ornithine, branched-chain amino acids, large neutral amino acids, essential amino acids, non-essential amino acids, basic amino acids, and arginine/ornithine ratio) were found to differ between healthy postmenopausal women and postmenopausal women with fibromyalgia, but not between healthy premenopausal women and premenopausal women with fibromyalgia. No significant differences were found in serum amino acid concentrations between premenopausal and postmenopausal healthy women or between premenopausal and postmenopausal women with fibromyalgia. Our results show, for the first time, that the association between menopause and fibromyalgia may increase the risk of metabolic disorders by disrupting amino acid homeostasis to a greater extent than menopause or fibromyalgia alone.

Antifatigue effect of okara protein hydrolysate supplementation during cycling exercise in men: a pre-post uncontrolled pilot study.

Prolonged exercise usually leads to exercise fatigue, which has a negative short-term impact on exercise performance and metabolic rate; thus, fatigue needs to be resolved. Okara is a protein-rich residue of soy processing. Enzyme hydrolysis is known to increase the content of branched-chain amino acids (BCAAs), which have been reported to confer benefits for exercise. The purpose of this study was to investigate the antifatigue effect of okara protein hydrolysate (OPH) on cycling exercise. A total of 16 male participants who habitually exercised (2 times or more per week and without participation in athletic contests) were instructed to receive 11.74 g of OPH once a day. They then completed two intense cycling exercise challenges before and after four weeks of supplementation. Exercise time and blood markers related to fatigue and energy metabolism were measured. The results showed that the time to exhaustion significantly increased after the treatment. The levels of lactate during exercise and at the end of exercise were significantly lower after treatment than before. Additionally, postexercise insulin sensitivity was increased after treatment. This study showed that OPH supplementation can promote endurance in exercise by decreasing the accumulation of fatigue-related metabolites during exercise and can promote energy recovery by increasing insulin function. These findings suggest that OPH has an antifatigue property.

Dephosphorylation of branched-chain α-keto acid dehydrogenase E1α (BCKDHA) promotes branched-chain amino acid catabolism and renders cancer cells resistant to X-rays by mitigating DNA damage

Dephosphorylation of branched-chain α-keto acid dehydrogenase E1α (BCKDHA) promotes branched-chain amino acid catabolism and renders cancer cells resistant to X-rays by mitigating DNA damage

Tailored impact of dietary fibers on gut microbiota: a multi-omics comparison on the lean and obese microbial communities

BackgroundPrevious studies have shown that microbial communities differ in obese and lean individuals, and dietary fiber can help reduce obesity-related conditions through diet-gut microbiota interactions. However, the mechanisms by which dietary fibers shape the gut microbiota still need to be elucidated. In this in vitro study, we examined how apple fibers affect lean and obese microbial communities on a global scale. We employed a high-throughput micro-matrix bioreactor system and a multi-omics approach to identify the key microorganisms and metabolites involved in this process.ResultsInitially, metagenomics and metabolomics data indicated that obese and lean microbial communities had distinct starting microbial communities. We found that obese microbial community had different characteristics, including higher levels of Ruminococcus bromii and lower levels of Faecalibacterium prausnitzii, along with an increased Firmicutes:Bacteroides ratio. Afterward, we exposed obese and lean microbial communities to an apple as a representative complex food matrix, apple pectin as a soluble fiber, and cellulose as an insoluble fiber. Dietary fibers, particularly apple pectin, reduced Acidaminococcus intestini and boosted Megasphaera and Akkermansia in the obese microbial community. Additionally, these fibers altered the production of metabolites, increasing beneficial indole microbial metabolites. Our results underscored the ability of apple and apple pectin to shape the obese gut microbiota.ConclusionWe found that the obese microbial community had higher branched-chain amino acid catabolism and hexanoic acid production, potentially impacting energy balance. Apple dietary fibers, especially pectin, influenced the obese microbial community, altering both species and metabolites. Notably, the apple pectin feeding condition affected species like Klebsiella pneumoniae and Bifidobacterium longum. By using genome-scale metabolic modeling, we discovered a mutualistic cross-feeding relationship between Megasphaera sp. MJR8396C and Bifidobacterium adolescentis. This in vitro study suggests that incorporating apple fibers into the diets of obese individuals can help modify the composition of gut bacteria and improve metabolic health. This personalized approach could help mitigate the effects of obesity.1sSYKieb1FyPG4CFVZT5APVideo Graphical

Supplementation of diet with Astaxanthin and DHA prevents gestational and lactational undernourishment-induced metabolic derangements in dams: a metabolomic approach.

Nutrition is the critical nongenetic factor that has a major influence on the health status of an organism. The nutritional status of the mother during gestation and lactation plays a vital role in defining the offspring's health. Undernutrition during these critical periods may induce chronic metabolic disorders like obesity and cardiovascular diseases in mothers as well as in offspring. The present study aims to evaluate the impact of undernutrition during gestational and lactational periods on the plasma metabolic profile of dams. Additionally, we investigated the potential synergistic mitigating effects of astaxanthin and docosahexaenoic acid (DHA) on dysregulated plasma metabolic profiles. Evaluation of plasma lipid profile revealed that undernourishment resulted in elevated levels of total cholesterol, triglycerides, low density and very low-density lipoproteins in dams. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomics illustrated that pathways related to lipid metabolism, such as cholesterol metabolism, steroid biosynthesis and metabolism of amine-derived hormones, were dysregulated by undernourishment. Additionally, pathway enrichment analysis predicted that there is a high incidence of development of desmosterolosis, hypercholesterolaemia, lysosomal acid lipase deficiency and Smith-Lemli-Opitz syndrome in the offspring, reflecting predisposition in mothers. However, synergistic supplementation of astaxanthin and DHA ameliorated these adverse effects by regulating a separate set of metabolic pathways associated with lipid metabolism. They included branched chain amino acid degradation such as valine, leucine and isoleucine, metabolism of alpha-linolenic acid, lipoic acid, lysine degradation, biosynthesis, elongation and degradation of fatty acids.

Maple syrup urine disease diagnosed in a resource-limited setting in an infant in Nepal: a case report

BackgroundMaple Syrup Urine Disease (MSUD) is a rare inherited disorder of metabolism, which manifests early in life in classical forms. Recurrent illness and exertion aggravate neurotoxicity. This case highlights MSUD diagnosed in association with COVID-19 complications from Nepal.Case presentationWe present a case of a 4-month-old child with a biochemical diagnosis of flared-up MSUD. Initially presenting with chief complaints of fever, noisy breathing, chest retraction, cough along with lethargy and poor feeding since the first week of life, the child also had developmental delay with feeble neck holding and absent social smile. The child was diagnosed with COVID-19 pneumonia and admitted in the Intensive Care Unit, requiring mechanical ventilation for 12 days. Despite the clinical resolution of pneumonia, the child had multiple episodes of generalized seizures and was sickly and frail. An incessant peculiar odor emanating from the child led to strong suspicion of metabolic disorder. Qualitative screening for amino acids (FeCl3 and 2,4-dinitrophenylhdrazine/DNPH) in urine and further gas chromatography-mass spectrometry revealed increased branched-chain amino acids(valine, leucine, and isoleucine). With dietary restrictions, the child was doing well. However, unfortunately, after 10 days of discharge, the child succumbed to death.ConclusionsThis case highlights the outpouring of hidden metabolic disorders with the onset of new diseases. It could have been detected and managed earlier with expedited neonatal screening and proper intervention.

Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging.

Restricting the intake of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan in young or adult mice. However, their effects when initiated in aged animals are unknown. Here we investigate the consequences of consuming a diet with 67% reduction of all amino acids (low AA) or of isoleucine alone (low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. Both dietary regimens effectively promote overall metabolic health without reducing calorie intake. Both low AA and low Ile diets improve aspects of frailty and slow multiple molecular indicators of aging rate; however, the low Ile diet reduces grip strength in both sexes and has mixed, sexually dimorphic effects on the heart. These results demonstrate that low AA and low Ile diets can promote aspects of healthy aging in aged mice and suggest that similar interventions might promote healthy aging in older adults.

Increased rumen Prevotella enhances BCAA synthesis, leading to synergistically increased skeletal muscle in myostatin-knockout cattle

Myostatin (MSTN) is a negative regulator of muscle growth, and its relationship with the gut microbiota is not well understood. In this study, we observed increase muscle area and branched-chain amino acids (BCAAs), an energy source of muscle, in myostatin knockout (MSTN-KO) cattle. To explore the link between increased BCAAs and rumen microbiota, we performed metagenomic sequencing, metabolome analysis of rumen fluid, and muscle transcriptomics. MSTN-KO cattle showed a significant increase in the phylum Bacteroidota (formerly Bacteroidetes), particularly the genus Prevotella (P = 3.12e-04). Within this genus, Prevotella_sp._CAG:732, Prevotella_sp._MSX73, and Prevotella_sp._MA2016 showed significant upregulation of genes related to BCAA synthesis. Functional enrichment analysis indicated enrichment of BCAA synthesis-related pathways in both rumen metagenomes and metabolomes. Additionally, muscle transcriptomics indicated enrichment in muscle fiber and amino acid metabolism, with upregulation of solute carrier family genes, enhancing BCAA transport. These findings suggest that elevated rumen Prevotella in MSTN-KO cattle, combined with MSTN deletion, synergistically improves muscle growth through enhanced BCAA synthesis and transport.