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Branched-chain amino acids (BCAA) and carbohydrate (CHO) are commonly recommended postexercise supplements. However, no study has examined the interaction of CHO and BCAA ingestion on myofibrillar protein synthesis (MyoPS) rates following exercise. We aimed to determine the response of MyoPS to the co-ingestion of BCAA and CHO following an acute bout of resistance exercise. Ten resistance-trained young men completed two trials in counterbalanced order, ingesting isocaloric drinks containing either 30.6-g CHO plus 5.6-g BCAA (B + C) or 34.7-g CHO alone following a bout of unilateral, leg resistance exercise. MyoPS was measured postexercise with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre- and 4 hr postdrink ingestion. Blood samples were collected at time points before and after drink ingestion. Serum insulin concentrations increased to a similar extent in both trials (p >.05), peaking at 30 min postdrink ingestion. Plasma leucine (514 ± 34 nmol/L), isoleucine (282 ± 23 nmol/L), and valine (687 ± 33 nmol/L) concentrations peaked at 0.5 hr postdrink in B + C and remained elevated for 3 hr during exercise recovery. MyoPS was ∼15% greater (95% confidence interval [−0.002, 0.028], p =.039, Cohen's d = 0.63) in B + C (0.128%/hr ± 0.011%/hr) than CHO alone (0.115%/hr ± 0.011%/hr) over the 4 hr postexercise period. Co-ingestion of BCAA and CHO augments the acute response of MyoPS to resistance exercise in trained young males. [ABSTRACT FROM AUTHOR]

Summary: In this study, we examined the physicochemical and functional properties of fava bean globulin fractions that are rich in legumin or vicilin proteins. The sulphur containing amino acids, branched chain amino acids, and arginine/lysine ratio obtained for legumin (1.89%, 18.32%, and 1.43%) are significantly (P < 0.05) higher than the 1.24%, 17.94%, and 1.05%, respectively, for the vicilin fraction. SDS‐PAGE results show that the legumin fraction had a wider range of polypeptide sizes (approximately 14–140 kDa) when compared to the approximately 12–68 kDa for vicilin. The surface hydrophobicity (So) of legumin (86.07) was significantly (P < 0.05) lower compared with vicilin (118.19). The legumin had higher protein solubility (approximately 40–50%) than the vicilin (0%) at pH 3 and 4, but vicilin solubility was higher at pH 6–8. The vicilin had higher (83.58%) in vitro protein digestibility than the legumin (78.24%). However, the legumin had higher oil‐holding capacity, lower least gelation concentration, and formed emulsions at pH 3, 7, and 9 with smaller mean oil droplet sizes than the vicilin. Foam formation was better with increased levels of α‐helix secondary structure. We conclude that pH of the environment was a stronger determinant of protein functionality than the sample protein concentration. [ABSTRACT FROM AUTHOR]

While it is generally known that metabolic disorders and circadian dysfunction are intertwined, how the two systems affect each other is not well understood, nor are the genetic factors that might exacerbate this pathological interaction. Blood chemistry is profoundly changed in metabolic disorders, and we have previously shown that serum factors change cellular clock properties. To investigate if circulating factors altered in metabolic disorders have circadian modifying effects, and whether these effects are of genetic origin, we measured circadian rhythms in U2OS cell in the presence of serum collected from diabetic, obese or control subjects. We observed that circadian period lengthening in U2OS cells was associated with serum chemistry that is characteristic of insulin resistance. Characterizing the genetic variants that altered circadian period length by genome‐wide association analysis, we found that one of the top variants mapped to the E3 ubiquitin ligase MARCH1 involved in insulin sensitivity. Confirming our data, the serum circadian modifying variants were also enriched in type 2 diabetes and chronotype variants identified in the UK Biobank cohort. Finally, to identify serum factors that might be involved in period lengthening, we performed detailed metabolomics and found that the circadian modifying variants are particularly associated with branched chain amino acids, whose levels are known to correlate with diabetes and insulin resistance. Overall, our multi‐omics data showed comprehensively that systemic factors serve as a path through which metabolic disorders influence circadian system, and these can be examined in human populations directly by simple cellular assays in common cultured cells. [ABSTRACT FROM AUTHOR]

This study set out to provide a preliminary assessment of nutritional profiles of five selected New Zealand macroalgae to investigate the potential of landcultivated Ulva spp. The New Zealand seaweeds species, selected from a limited range, were either collected from the wild (Pyropia plicata from Tauranga and Kaikōura), or were sourced from commercial wild harvest suppliers (Macrocystis pyrifera and Undaria pinnatifida), and were compared to land-based cultivated Ulva species (Ulva ralfsii and Ulva stenophylloides). Species were assessed for their content of crude protein, total lipids, carbohydrates, fibers, amino acids, mineral profiles, heavy metals and antioxidant capacity (Oxygen Radical Absorbance Capacity, ORAC). The two cultivated Ulva spp. had the highest crude protein content of the six seaweeds analyzed (approximately 21% dw, N×6.25), as expected with nutrient supplemented cultivation. They also had the highest total, essential and branched chain amino acid quantities (151, 70, and 29 mg/g for U. stenophylloides and 138, 62, and 27 mg/g for U. ralfsii). Though the two Ulva spp. were grown to the same cultivation specifications, they varied in carbohydrate and total fiber content (U. stenophylloides: 63% and 62%; U. ralfsii: 39% and 40%, respectively). Pyropia plicata collected in Kaikōura had the highest carbohydrate levels (65%) though not the highest total fiber. Both P. plicata had the highest trace minerals (417 mg/kg and 720 mg/kg for Kaikōura and Tauranga P. plicata respectively). All seaweeds analyzed showed no lipophilic antioxidants, though the two Phaeophyceae had the highest hydrophilic antioxidant content at 115 TE and 168 TE for Macrocystis pyrifera and Undaria pinnatifida, respectively. This paper provides a preliminary indication of the relative nutritional attributes of a range of potential New Zealand seaweed aquaculture targets benchmarked against sealettuce (Ulva spp.). [ABSTRACT FROM AUTHOR]

\n In experimental and observational studies, the characteristics of gut microbiota have been associated with Parkinson’s disease (PD), among which metabolic pathways played an important role. However, the causality remained unclear.Herein, we aimed to determine the potential impact of gut microbiota and gut microbiota-derived metabolites on PD risk using a Mendelian randomization (MR) approach.We included as exposures gut microbial taxa abundance and gut-derived metabolites (branched chain amino acids [BCAAs]), with PD as the outcome. In addition, we explored whether BCAAs act as a mediating factor in the pathway from gut microbiota to PD.We found evidence of a causality of 15 microbial taxa and PD before and after sensitivity analyses, but not after multiple testing correction. There was significant association between BCAAs levels and the risk of PD, especially isoleucine (OR = 0.995, 95% CI 0.992–0.999, p = 0.004, pFDR = 0.012). In addition, the causality of gut microbiota and BCAAs was also explored that the increased g_Coprococcus abundance can result in the decrease in isoleucine level (OR = 1.046; 95% CI, 1.009–1.085; p = 0.016).Our findings indicated suggestive association between gut microbiota and its metabolites and PD. Furthermore, higher BCAAs levels were associated with the decreased PD risk. This study may provide new targets for PD treatment, such as dietary BCAAs supplementation.Dysbiosis of gut microbiota and its metabolites (branched chain amino acids, BCAAs) appears to be a related risk factor for Parkinson’s disease (PD). Thus far, studies mostly focused on cross-sectional observational studies of gut microbiota and its metabolites, but this Mendelian randomization analysis evaluated the potential impact of gut microbiota and gut microbiota derived metabolites (BCAAs) on PD risk. Gut microbiota and BCAAs as exposures and PD as outcome, it was found that there was no significant correlation between gut microbiota and PD, while increasing levels of BCAAs, especially isoleucine, increased the risk of PD. In addition, we also demonstrated that BCAAs could play a role in PD relying on the gut microbiota. For example, an increase in g-Coprococcus abundance can lead to a decrease in isoleucine levels in PD. Therefore, in the future, the PD risk may be reduced by maintaining the homeostasis of gut microbiota and its metabolites. [ABSTRACT FROM AUTHOR]

In this study, we explored the effects of chronic stress on lumpfish (Cyclopterus lumpus) physiological, immune response, health, and plasma free amino acids. 3 groups of lumpfish were exposed to 1-minute air exposure. 1 group was exposed to stress once per week, a second group exposed 2 times per week, and a third group exposed 4 times per week. The present study revealed significant alterations in immunity and increased nutritional demands, particularly the branched chain amino acids and lysine. Cortisol levels fluctuated, with significantly higher levels halfway through the experiment on the groups that were stressed more often. Though, by the end of the experiment, there were no significant differences in cortisol levels between groups. Regardless of stress exposure, cataract developed in virtually all sampled fish, pointing toward a potential dietary imbalance. A transient immunomodulation of stress was visible. While in early stages stress had an immune enhancing effect, as seen by the increase in plasma nitric oxide and peroxidase in the group most frequently exposed to stress, these differences were not apparent by the end of the experiment. Additionally, the worst health condition was found in this group. Our results underscore the complex interplay between stress, immunity and nutrition, highlighting the need for tailored dietary strategies and improved rearing practices. [ABSTRACT FROM AUTHOR]

Nowadays, the wine industry carries out fermentations at low temperatures because this oenological practice clearly improves the aromatic complexity of the final wines. In addition, nitrogen content of the must also influences the quality of the wine. In this study, we carried out a phenotypic and fermentative analysis of two industrial wine Saccharomyces cerevisiae strains (P5 and P24) at 15 and 28 °C and three nitrogen concentrations (60, 140 and 300 mg N/L) in synthetic must. Our results show that both parameters, temperature and nitrogen, are interrelated and clearly determine the competitiveness of the wine strains and their ability to adapt at low temperatures. The best adapted strain at low temperatures decreased its competitiveness at lower nitrogen concentrations. In addition, our results show that it is not only the quantity of nitrogen transported that is important but also the quality of the nitrogen source used for wine yeast adaptation at low temperatures. The presence of some amino acids, such as arginine, branched chain amino acids, and some aromatic amino acids can improve the growth and fermentation activity of wine yeasts at low temperatures. These results allow us to better understand the basis of wine yeast adaptation to fermentation conditions, providing important information for winemakers to help them select the most appropriate yeast strain, thus reducing the economic costs associated with long and sluggish fermentations. The correlation between some amino acids and better yeast fermentation performance could be used in the future to design inactive dry yeast enriched in some of these amino acids, which could be added as a nutritional supplement during low temperature fermentations. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations between dietary/serum branched-chain amino acids (BCAAs) and cardiometabolic risk markers. Methods: In a cohort of 2791 participants, diet and cardiometabolic risk markers were measured twice at baseline in overall participants and after 1-year in a subset of 423 participants. We assessed serum BCAAs at baseline and arterial stiffness after 1-year. The cross-sectional associations between dietary/serum BCAAs and cardiometabolic risk markers were analyzed using baseline measurements by linear regression, while the 1-year longitudinal association were analyzed using repeated measurements by linear mixed-effects regression. Results: Higher BCAA intake from poultry was associated with lower triglycerides (β=-0.028, P = 0.027) and higher high-density lipoprotein cholesterol (HDL-C, β = 0.013, P = 0.006), while BCAAs in red and processed meat or fish were inversely associated with low-density lipoprotein cholesterol (β = 0.025, P = 0.001) and total cholesterol (β = 0.012, P = 0.033), respectively. BCAAs in whole grains and nuts were associated with higher HDL-C (β = 0.011, P = 0.016), and lower TG (β=-0.021, P = 0.041) and diastolic blood pressure (β=-0.003, P = 0.027). Also, BCAAs from soy or vegetables and fruits were inversely associated with arterial stiffness (β=-0.018, P = 0.047) and systolic blood pressure (β=-0.011, P = 0.003), respectively. However, BCAAs in refined grains were positively associated with triglycerides (β = 0.037, P = 0.014). Total serum BCAAs were unfavorably associated with multiple cardiometabolic risk markers (all P < 0.05). Conclusion: Dietary BCAAs in poultry, whole grains and nuts, soy, and vegetables and fruits may be favorably, while BCAAs in red and processed meat, fish, and refined grains were unfavorably associated with cardiometabolic health. Serum BCAAs showed a detrimental association with cardiometabolic risk markers. [ABSTRACT FROM AUTHOR]

• Serum branched chain amino acids (BCAAs) were unfavorably correlated with obesity. • Dietary BCAA intake was associated with increase in body fat measures. • Dietary BCAAs show a weak correlation with circulating BCAA concentrations. Animal studies showed a detrimental effect of dietary branched chain amino acids (BCAAs) on metabolic health, while epidemiological evidence on dietary BCAAs and obesity is limited and inconclusive. We hypothesized that high dietary and circulating BCAAs are unfavorably associated with obesity in community-dwelling adults. We evaluated the 1-year longitudinal associations of dietary BCAA intake and circulating BCAAs with body fat measures. Body weight, height, and circumferences of the waist (WC) and hip (HC) were measured at baseline and again after 1-year. Body composition and liver fat [indicated by controlled attenuation parameter (CAP)] were also assessed after 1-year. Serum BCAA concentrations at baseline were quantified by liquid chromatography mass spectrometry. Diet was collected using 4 quarterly 3-day recalls during the 1-year. The correlation coefficients between dietary and serum BCAAs were 0.12 (P =.035) for total dietary BCAAs, and ranged from -0.02 (soy foods, P =.749) to 0.18 (poultry, P =.001). Total dietary BCAA intake was associated with increase in body weight (β = 0.044, P =.022) and body mass index (BMI, β = 0.047, P =.043). BCAAs from animal foods were associated with increase in HC, while BCAAs from soy foods were associated with weight gain and higher CAP (all P <.05). Serum BCAAs were associated with higher WC, HC, BMI, body fat mass, visceral fat level, and CAP (all P <.05). These results support that dietary and circulating BCAAs are positively associated with the risk of obesity. More cohort studies with validated dietary assessment tools and long-term follow-up among diverse populations are needed to confirm our findings. We evaluated the longitudinal associations of dietary and circulating BCAAs with body fat measures in Chinese population. Despite a weak correlation between dietary and circulating BCAAs, both total dietary BCAAs and circulating BCAAs showed an unfavorable impact on multiple body fat measures in the population. BCAAs, branched chain amino acids. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: In this pilot study, we used untargeted metabolomics to identify biochemical mechanisms or biomarkers potentially underlying SLE-related fatigue. Methods: Metabolon conducted untargeted metabolomic plasma profiling using ultrahigh performance liquid chromatography/tandem mass spectrometry on plasma samples of 23 Black females with systemic lupus erythematosus (SLE) and 21 no SLE controls. Fatigue phenotypes of general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation were measured with the reliable and valid Multidimensional Fatigue Inventory (MFI). Results: A total of 290 metabolites were significantly different between the SLE and no SLE groups, encompassing metabolites related to glycolysis, TCA cycle activity, heme catabolism, branched chain amino acids, fatty acid metabolism, and steroids. Within the SLE group, controlling for age and co-morbidities, TCA cycle metabolites of alpha-ketoglutarate (AKG) and succinate were statistically significantly associated (p <.05) with physical and general fatigue. Conclusion: While pervasive perturbations in the entire TCA cycle have been implicated as a potential mechanism for fatigue, our results suggest individual metabolites of AKG and succinate may be potential biomarkers or targets of intervention for fatigue symptom management in SLE. Additionally, perturbations in heme metabolism in the SLE group provide additional insights into mechanisms that promote systemic inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Thiamine (Vitamin B1) is an essential micronutrient and is classically considered a co-factor in energy metabolism. The association between thiamine status and whole-body metabolism in critical illness has not been studied. Objectives: To determine association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites and connected metabolic pathways using high resolution metabolomics (HRM) in critically ill patients. Methods: Cross-sectional study performed at Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were critically ill adults with an expected length of intensive care unit stay longer than 48 h and receiving chronic furosemide therapy. A total of 76 participants were included. Mean age was 69 years (range 33–92 years); 65% were female. Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP was measured by HPLC and plasma HRM was performed using liquid chromatography/mass spectrometry. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies (MWAS). MWAS using the highest and lowest TPP concentration tertiles was performed as a secondary analysis. Results: Specific metabolic pathways associated with whole blood TPP levels in regression and tertile analysis included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways. Conclusions: Plasma HRM revealed that thiamine status, determined by whole blood TPP concentrations, was significantly associated with metabolites and metabolic pathways related to metabolism of energy, carbohydrates, amino acids, lipids, and the gut microbiome in adult critically ill patients. [ABSTRACT FROM AUTHOR]

Background: The association of BCAAs (isoleucine, leucine, and valine) with cardiovascular and cerebrovascular diseases has been widely recognized by researchers, but there is limited evidence to support the relationship between BCAAs and multiple chronic conditions (MCCs) in older adults. This study aimed to explore the correlation between BCAA levels in the diets of older adults and MCCs. Methods: Based on a health management cohort project in Nanshan District of Shenzhen, 4278 individuals over 65 years old were selected as participants via multi-stage stratified sampling from May 2018 to December 2019. Data were collected using a validated semi-quantitative food frequency questionnaire, as well as anthropometric and chronic disease reports. MCC was defined as the coexistence of two or more chronic diseases, namely, hypertension, dyslipidemia, diabetes, CAD, stroke, CKD, and CLD. Multivariate unconditional logistic regression analysis was used to analyze the relationship between dietary BCAAs and MCCs in older adults, and then, gender stratification analysis was performed. A restricted cubic spline model (a fitted smooth curve) was used to determine the dose–response relationship of isoleucine with MCCs. Results: A total of 4278 older adults aged 65 and above were included in this study, with an average age of 72.73 ± 5.49 years. The cohort included 1861 males (43.50%). Regardless of whether confounding factors were corrected, isoleucine was a risk factor for MCCs (OR = 3.388, 95%CI:1.415,8.109). After gender stratification, the relationships between dietary isoleucine and MCCs (OR = 6.902, 95%CI:1.875,25.402) and between leucine (OR = 0.506,95%CI:0.309,0.830) and MCCs were significant in women, but not in men. No significant association between valine and MCCs was observed. In addition, isoleucine was a risk factor for MCCs when its intake was greater than 4.297 g/d. Conclusion: Isoleucine may play an important role in regulating age-related diseases. BCAAs such as isoleucine can be used as risk markers for MCCs in older adults. [ABSTRACT FROM AUTHOR]

Type-2 diabetes (T2D) is a rapidly growing multifactorial metabolic disorder that induces the onset of various diseases in the human body. The compositional and metabolic shift of the gut microbiota is a crucial factor behind T2D. Hence, gaining insight into the metabolic profile of the gut microbiota is essential for revealing their role in regulating the metabolism of T2D patients. Here, we have focused on the genome-scale community metabolic model reconstruction of crucial T2D-associated gut microbes. The model-based analysis of biochemical flux in T2D and healthy gut conditions showed distinct biochemical signatures and diverse metabolic interactions in the microbial community. The metabolic interactions encompass cross-feeding of short-chain fatty acids, amino acids, and vitamins among individual microbes within the community. In T2D conditions, a reduction in the metabolic flux of acetate, butyrate, vitamin B5, and bicarbonate was observed in the microbial community model, which can impact carbohydrate metabolism. The decline in butyrate levels is correlated with both insulin resistance and diminished glucose metabolism in T2D patients. Compared to the healthy gut, an overall reduction in glucose consumption and SCFA production flux was estimated in the T2D gut environment. Moreover, the decreased consumption profiles of branch chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the T2D gut microbiota can be a distinct biomarker for T2D. Hence, the flux-level analysis of the microbial community model can provide insights into the metabolic reprogramming in diabetic gut microbiomes, which may be helpful in personalized therapeutics and diet design against T2D. [ABSTRACT FROM AUTHOR]

Global warming has led to the expansion of arid lands and more frequent droughts, which are the largest cause of global food production losses. In our previous study, we developed TaPYLox wheat overexpressing the plant hormone abscisic acid (ABA) receptor, which is important for the drought stress response in plants. TaPYLox showed resistance to drought stress and acquired water-saving traits that enable efficient grain production with less water use. In this study, we used TaPYLox to identify ABA-dependent and -independent metabolites in response to drought stress. We compared the variation of metabolites in wheat under well-watered, ABA treatment, and drought stress conditions using the ABA-sensitive TaPYLox line and control lines. The results showed that tagatose and L-serine were ABA-dependently regulated metabolites, because their stress-induced accumulation was increased by ABA treatment in TaPYLox. In contrast, L-valine, L-leucine, and DL-isoleucine, which are classified as branched chain amino acids, were not increased by ABA treatment in TaPYLox, suggesting that they are metabolites regulated in an ABA-independent manner. Interestingly, the accumulation of L-valine, L-leucine, and DL-isoleucine was suppressed in drought-tolerant TaPYLox under drought stress, suggesting that drought-tolerant wheat might be low in these amino acids. 3-dehydroshikimic acid and α-ketoglutaric acid were decreased by drought stress in an ABA-independent manner. In this study, we have succeeded in identifying metabolites that are regulated by drought stress in an ABA-dependent and -independent manner. The findings of this study should be useful for future breeding of drought-tolerant wheat. [ABSTRACT FROM AUTHOR]

Muscle wasting can be caused by nutrition deficiency and inefficient metabolism of amino acids, including Branched Chain Amino Acids (BCAAs). Branched Chain Amino Acids are a major contributor to the metabolic needs of healthy muscle and account for over a tenth of lean muscle mass. Branched chain alpha-ketoacid dehydrogenase (BCKD) is the rate limiting enzyme of BCAA metabolism. Inhibition of BCKD is achieved through a reversible phosphorylation event by Branched Chain a-ketoacid dehydrogenase kinase (BCKDK). Our study set out to determine the importance of BCKDK in the maintenance of skeletal muscle. We used the Gene Expression Omnibus Database to understand the role of BCKDK in skeletal muscle pathogenesis, including aging, muscular disease, and interrupted muscle metabolism. We found BCKDK expression levels were consistently decreased in pathologic conditions. These results were most consistent when exploring muscular disease followed by aging. Based on our findings, we hypothesize that decreased BCKDK expression alters BCAA catabolism and impacts loss of normal muscle integrity and function. Further research could offer valuable insights into potential therapeutic strategies for addressing muscle-related disorders. [ABSTRACT FROM AUTHOR]

Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research. [ABSTRACT FROM AUTHOR]

Thioredoxins (TRXs) are central to redox regulation, modulating enzyme activities to adapt metabolism to environmental changes. Previous research emphasized mitochondrial and microsomal TRX o1 and h2 influence on mitochondrial metabolism, including photorespiration and the tricarboxylic acid (TCA) cycle. Our study aimed to compare TRX‐based regulation circuits towards environmental cues mainly affecting photorespiration. Metabolite snapshots, phenotypes and CO2 assimilation were compared among single and multiple TRX mutants in the wild‐type and the glycine decarboxylase T‐protein knockdown (gldt1) background. Our analyses provided evidence for additive negative effects of combined TRX o1 and h2 deficiency on growth and photosynthesis. Especially metabolite accumulation patterns suggest a shared regulation mechanism mainly on mitochondrial dihydrolipoamide dehydrogenase (mtLPD1)‐dependent pathways. Quantification of pyridine nucleotides, in conjunction with 13C‐labelling approaches, and biochemical analysis of recombinant mtLPD1 supported this. It also revealed mtLPD1 inhibition by NADH, pointing at an additional measure to fine‐tune it's activity. Collectively, we propose that lack of TRX o1 and h2 perturbs the mitochondrial redox state, which impacts on other pathways through shifts in the NADH/NAD+ ratio via mtLPD1. This regulation module might represent a node for simultaneous adjustments of photorespiration, the TCA cycle and branched chain amino acid degradation under fluctuating environmental conditions. Summary statement: Thioredoxins o1 and h2 concertedly adapt the performance of mtLPD1‐dependent pathways towards short‐ and long‐term environmental changes. Simultaneous adjustments of mitochondrial pathway fluxes are achieved through fine tuning of mtLPD1 activity via redox regulation and subcellular NADH/NAD+ ratios. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a metabolic chronic disease in which insulin resistance and insufficient insulin production lead to elevated blood glucose levels. The prevalence of T2D is growing worldwide, mainly due to obesity and the adoption of Western diets. Replacing animal foods with healthy plant foods is associated with a lower risk of T2D in prospective studies. In randomized controlled trials, the consumption of healthy plant foods in place of animal foods led to cardiometabolic improvements in patients with T2D or who were at high risk of the disease. Dietary patterns that limit or exclude animal foods and focus on healthy plant foods (eg, fruits, vegetables, whole grains, nuts, legumes), known as healthy, plant-based diets, are consistently associated with a lower risk of T2D in cohort studies. The aim of this review is to examine the differential effects of plant foods and animal foods on T2D risk and to describe the existing literature about the role of healthy, plant-based diets, particularly healthy vegan diets, in T2D prevention and management. The evidence from cohort studies and randomized controlled trials will be reported, in addition to the potential biological mechanisms that seem to be involved. [ABSTRACT FROM AUTHOR]

To explore the differences in the composition, content and comprehensive quality of free amino acids (FAA) in millet from Longzhong area in Gansu Province, 12 different cultivars of millet were used as research objects, the types and contents of FAA were determined by liquid chromatography-tandem mass spectrometry. Comprehensive evaluation of FAA quality was performed by principal component analysis (PCA) and hierarchical cluster analysis (HCA). The results showed that 19-20 kinds of FAA were detected in all kinds of millet, and the total content of FAA ranged from 1046.80-1773.85 mg/kg, asparagine (Asn), aspartic acid (Asp), glutamic acid (Glu) and glycine (Gly) were the four main FAA in millet. There were significant differences in the contents of FAA (P<0.05), but no obvious difference in types in the 12 cultivars of millet. The characteristics of flavor amino acids in millet were delicious amino acids>bitter amino acids>sweet amino acids>aromatic amino acids. 9 Medicinal amino acids and 3 branched chain amino acids were found in millet, the average content of medicinal amino acids was 706.34 mg/kg, the percentages of medicinal amino acids to total FAA was 53.63%, so millet had many potential medicinal values. There was a significant relation with FAA in different cultivars of millet, five principal components were extracted after PCA, and the cumulative contribution ratio of the five components was 86.20%, the FAA comprehensive scores of LG-23, LG-11 and YG-18 were ranked as the top three. The 12 different cultivars millet were divided into four groups by HCA, FAA comprehensive quality performances of groups I (LG-23) and III (LG-11 and YG-18) were optimal, the content of total FAA was significantly higher than the other two groups (P<0.05), but group II (HNLG, LG-18, LG-029) had relatively poor FAA quality, and the results were consistent with the PCA, which reflected the distinction among different cultivars of millet. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew's correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model. [ABSTRACT FROM AUTHOR]

Aim: Branched‐chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. Methods: During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan–Meier analyses were conducted to examine time‐dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. Results: The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. Conclusions: Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; 24: 603–608. [ABSTRACT FROM AUTHOR]

Aim: Frailty is defined as extreme vulnerability, a syndrome that exposes the individual to a higher risk of disability. While risk factors for frailty have been gradually uncovered, the full identification of biochemical factors and co‐morbidities influencing frailty remains incomplete. Methods: Cross‐sectional and longitudinal analyses were performed to elucidate the risk factors for the prevalence and progression of frailty. The study included 1035 Japanese female outpatients. At baseline, biochemical markers were measured. Co‐morbidities included diabetes mellitus, dyslipidemia, hypertension, vertebral osteoarthritis, and osteoporosis. Frailty levels were assessed using frailty scores ranging from 0 to 5. Prevalence of frailty was judged by a score of 3 or above, and progression was judged by an increase in the frailty score during the observation period. Multiple regression analysis was used for the cross‐sectional analysis, and the Cox hazard model was used for the longitudinal analysis. Results: Of the 1035 selected participants, 212 were diagnosed with frailty. Advanced age and log IL‐6 and branched‐chain amino acids (BCAA) levels were significant independent risk factors for frailty. Subjects were followed for 7.7 ± 5.9 years and progression was observed in 130 subjects. Older age, the absence of hyperlipidemia, the presence of osteoporosis, and lower frailty scores were identified as significant risk factors for frailty progression. Conclusions: Inflammatory and nutritional markers exhibited significant associations with the current frailty status, whereas co‐morbidities such as osteoporosis or hyperlipidemia emerged as independent risk or protective factors of future frailty progression. Geriatr Gerontol Int 2024; 24: 523–528. [ABSTRACT FROM AUTHOR]

Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11–34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between June 24, 2014 and December 5, 2020. Participants were randomized to one of five study arms (placebo and 15 g, 30 g, 45 g, and 54 g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms; however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0–54 scale for every 500 g of study drug consumed, p value for trend = 0.0036, [uncorrected]) and return to physical activity (increase of 0.503 points on a 0–5 scale for every 500 g of study drug consumed, p value for trend = 0.005 [uncorrected]). There were no serious adverse events. Eight of 38 participants reported a mild (not interfering with daily activity) or moderate (limitation of daily activity) adverse event; there were no differences in adverse events by arm, with only two reported mild adverse events (both gastrointestinal) in the highest (45 g and 54 g) BCAA arms. Although limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability, of BCAAs in concussed adolescents and young adults; specifically, a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery. [ABSTRACT FROM AUTHOR]

We aimed to investigate the intricate interplay between genetic predisposition and lifestyle factors on stroke. We conducted a comprehensive genome-wide association study to identify the genetic variants linked to stroke in the participants who experienced a stroke event (cases; n 672) and those with no stroke history (non-stroke; n 58 029) in a large hospital-based cohort. Using generalised multifactor dimensionality reduction, we identified genetic variants with interactive effects and constructed polygenic risk scores (PRS) by summing up the risk alleles from the genetic variants. Food intake was measured with a validated semi-quantitative FFQ. No significant differences in stroke incidence were seen in demographic variables between the two groups. Among the metabolic indicators, only serum TAG levels were higher in males with stroke than those without stroke. The daily nutrient intake, dietary inflammation index, glycaemic index, dietary patterns, alcohol consumption, exercise and smoking did not display associations with the OR for stroke. The stroke-linked genetic variants were related to the IL - 18 pathway. After accounting for covariates, the PRS derived from the 5-, 6- and 7-SNP models were positively associated with stroke chance with 2·5-, 2·9- and 2·8-fold. Furthermore, interactions between genetic predisposition and dietary components, including energy, carbohydrates, n -3 fatty acids and branched-chain amino acids (BCAA), that affected OR for stroke were observed. A high intake of energy, carbohydrates and BCAA and a low intake of n -3 fatty acids were positively associated with the chances of stroke occurrence. In conclusion, understanding the interaction between genetic variants and lifestyle factors can assist in developing stroke prevention and management strategies. [ABSTRACT FROM AUTHOR]

Background: This study examines the association between micronutrient intake, anthropometric indices, lipid accumulation, and blood lipid risk index among Tehranian women. Methods: A cross‐sectional study was conducted on 556 Tehranian women. Dietary intake was measured using a Food Frequency Questionnaire. Biochemical assessment and anthropometric indices were measured, and demographic information and physical activity were collected. Results: Participants with the highest intake of carbohydrates were more prone to obesity. Conversely, those in the top tertile for protein intake had a lower likelihood of obesity and higher levels of lipid accumulation product (LAP). The highest fat consumers had a 63% decreased chance of having a high Castelli's Risk Index 1 (CRI‐1). A higher glycemic index (GI) and glycemic load (GL) were linked to an increased probability of a high atherogenic coefficient (AC). Women in the top tertile of GL were significantly more likely to be obese and had lower odds for high LAP. Participants in the top tertile of aromatic amino acids/branched chain amino acids (AAA/BCAA) had significantly lower chances of high CRI‐1 and a high atherogenic index of plasma (AIP). Those in the highest tertile of monounsaturated fatty acids/polyunsaturated fatty acids (MUFA/PUFA) had lower odds of obesity and high AIP. Conclusions: The amount of carbohydrate (g) and protein intake (%), dietary GL, and the ratio of MUFA to PUFA were associated with obesity. The amount of fat intake (g) and AAA/BCAA indices were associated with CRI‐1. LAP decreased with an increase in GL. AC increased with an increase in GI and GL. AAA/BCAA and MUFA/PUFA were associated with AIP. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine the association between blood levels of Branched-chain amino acids (BCAAs) - specifically isoleucine, leucine, and valine - and the susceptibility to three neurodegenerative disorders: dementia, Alzheimer's disease (AD), and Parkinson's disease (PD). Methods: Based on data from the UK Biobank, a Cox proportional hazard regression model and a dose-response relationship were used to analyze the association between BCAAs and the risks of dementia, AD, and PD. We also generated a healthy lifestyle score and a polygenic risk score. Besides, we conducted a sensitivity analysis to ensure the robustness of our findings. Results: After adjusting for multiple covariates, blood concentrations of isoleucine, leucine, and valine were significantly associated with a reduced risk of dementia and AD. This association remained robust even in sensitivity analyses. Similarly, higher levels of isoleucine and leucine in the blood were found to be associated with an increased risk of PD, but this positive correlation could potentially be explained by the presence of covariates. Further analysis using a dose-response approach revealed that a blood leucine concentration of 2.14 mmol/L was associated with the lowest risk of dementia. Conclusion: BCAAs have the potential to serve as a biomarker for dementia and AD. However, the specific mechanism through which BCAAs are linked to the development of dementia, AD, and PD remains unclear and necessitates additional investigation. [ABSTRACT FROM AUTHOR]

Background: Branched-chain amino acid (BCAA) supplementation is one of the most popular strategies used by the general population and athletes to reduce muscle soreness and accelerate the recovery process of muscle damage biomarkers after an intense exercise or training session. Objectives: This systematic review and meta-analysis investigated the effects of BCAA supplementation on muscle damage biomarkers and muscle soreness after exercise-induced muscle damage (EIMD). Methods: The systematic literature search for randomized controlled trials was conducted using seven databases, up to September 13th, 2022. The eligibility criteria for selecting studies were as follows: studies performed on healthy active participants, using BCAA at least once, controlled with a placebo or control group, performing resistance or endurance exercises, and followed up at least once post-EIMD. The methodological quality of the studies was assessed using the "SIGN RCT checklist". Random-effects meta-analyses were processed to compute the standardized mean difference (Hedges' g). Meta-regression analyses were completed with daily and total dosage and supplementation as continuous moderator variables. Results: Of the 18 studies included in this meta-analysis, 13 were of high quality and five were of acceptable quality. Our results revealed BCAA supplementation elicits a significant effect on reducing creatine kinase (CK) levels immediately (g = − 0.44; p = 0.006) and 72 h (g = − 0.99; p = 0.002), but not 24 h, 48 h, and 96 h post-EIMD. Additionally, a significant effect on delayed onset of muscle soreness (DOMS) was identified at 24 h (g = − 1.34; p < 0.001), 48 h (g = − 1.75; p < 0.001), 72 h (g = − 1.82; p < 0.001), and 96 h (g = − 0.82; p = 0.008), but not immediately post-EIMD. No significant effect was found on lactate dehydrogenase (LDH) levels at any time point. Meta-regression indicated higher daily and total dosages of BCAA, and longer supplementation periods were related to the largest beneficial effects on CK (total dosage and supplementation period) at 48 h, and on DOMS at 24 h (only daily dosage). Conclusion: The overall effects of BCAA supplementation could be considered useful for lowering CK and DOMS after EIMD, but not LDH. The longer supplementation period prior to the EIMD could be more effective for CK and DOMS reduction. Key Points: Branched-chain amino acid supplementation is likely to reduce muscle soreness and creatine kinase, but not lactate dehydrogenase. The responses of muscle damage biomarkers and muscle soreness to branched-chain amino acid supplementation may be influenced by study design, blinding, training status, and sex. Dose-response relationships revealed high daily doses of branched-chain amino acids, with a long supplementation period (i.e., > 7 days), could be more effective in lowering creatine kinase levels. A high total dosage of branched-chain amino acids (i.e., > 5 g/day) could be more effective in reducing muscle soreness. [ABSTRACT FROM AUTHOR]

Introduction: The increasing prevalence of high-intensity sports activities, notably the burgeoning popularity of CrossFit, underscores the contemporary significance of such physical pursuits. The discernible protective impact of branched-chain amino acids on muscle fatigue and injuries is emerging as a noteworthy area of investigation. Within the realm of sports, integrating BCAA supplementation into dietary practices holds promise for aiding athletes in their recovery, particularly in mitigating Delayed-Onset Muscle Soreness. Methodology: This study adopted an experimental pilot design with repeated measures, employing a controlled and randomized approach through double-blind procedures. The participant engaged in high-intensity activity, specifically the CrossFit Karen® test, which entailed executing 150 wall ball throws (9 kg) to a height of 3 m. The trial incorporated three randomized supplementation conditions: BCAAs in an 8:1:1 ratio or a 2:1:1 ratio or a placebo condition. The participant consumed 15 g daily for 7 days, commencing 72 h prior to the initial blood sample and the first Karen® test. Results: In this study, BCAA supplementation at an 8:1:1 ratio demonstrated a discernible protective effect against muscular damage, as evidenced by creatine kinase values and ratings of perceived exertion. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is characterized by elevated circulating blood metabolites such as glucose, insulin, and branched chain amino acids (BCAA), which often coincide with reduced mitochondrial function. 4-Phenylbutyrate (PBA), an ammonia scavenger, has been shown to activate BCAA metabolism, resolve endoplasmic reticulum (ER) stress, and rescue BCAA-mediated insulin resistance. To determine the effect of PBA on the altered metabolic phenotype featured in type 2 diabetes, the present study investigated the effect of PBA on various metabolic parameters including mitochondrial metabolism and mitochondrial biogenesis. C2C12 myotubes were treated with PBA at 0.5 mM (representing physiologically attainable blood concentrations) or 10 mM (representing physiologically unattainable/proof-of-concept levels) for up to 24 h. Mitochondrial and glycolytic metabolism were assessed via oxygen consumption and extracellular acidification rate, respectively. Mitochondrial content, lipid content, and ER stress were measured by fluorescent staining. Metabolic gene expression was measured by qRT-PCR. Both doses of PBA increased expression of indicators of mitochondrial biogenesis, though only PBA at 0.5 mM increased mitochondrial function and content while 10 mM PBA reduced mitochondrial function and content. PBA at 0.5 mM also rescued reduced mitochondrial function during insulin resistance, though PBA also caused a reduced insulin stimulated pAkt expression during insulin resistance. PBA treatment also increased extracellular BCAA accumulation during insulin resistance despite unchanged pBCKDH expression. Taken together, PBA may increase mitochondrial biogenesis, content, and function in a dose-dependent fashion which may have implications for prevention or treatment of metabolic disease such as insulin resistance. • 4-Phenylbutyrate dose-dependently increased myotube mitochondrial biogenesis and function. • 4-Phenylbutyrate rescued myotube mitochondrial function during insulin resistance. • Low-levels of 4-Phenylbutyrate increased extracellular BCAA accumulation during insulin resistance. [ABSTRACT FROM AUTHOR]

Diabetes is a widespread metabolic disorder and results from insulin resistance and impaired insulin secretion. Modifiable factors like diet, physical activity, and body weight play crucial roles in diabetes prevention, with targeted interventions reducing diabetes risk by about 60%. High-protein consumption, above the recommended intake of 0.8 g/kg body weight per day, have often explored in relation to diabetes risk. However, the relationship between dietary protein and diabetes is multifaceted. Observational studies have linked high total and animal protein intake to an increased risk of type 2 diabetes, particularly in obese women. Elevated levels of branched-chain amino acids (BCAA), which can result from dietary intake, protein breakdown, as well as an impaired catabolism, are strong predictors of cardiometabolic risk and insulin resistance. With several mechanism linking BCAA to insulin resistance. On the other hand, intervention studies suggest that high-protein diets can support weight loss and improve cardiometabolic risk factors. However, the impact on insulin sensitivity and glucose homeostasis is not straightforward. Proteins and amino acids stimulate both insulin and glucagon secretion, influencing glucose levels, but chronic effects remain uncertain. This short narrative review aims to provide an update on the relationship between increased dietary protein intake, amino acids, insulin resistance and type 2 diabetes, and to describe protein recommendations for type 2 diabetes.

The article explores the role of glycolysis in heart failure with preserved ejection fraction (HFpEF). It discusses a study that examines glycolytic intermediates and enzymes in HFpEF patients, finding decreased levels of intermediates and reduced expression of synthesizing enzymes. The article also discusses other studies that suggest impaired glycolysis and glucose metabolism in HFpEF. It emphasizes the need for further research and potential therapeutic strategies targeting metabolic pathways for HFpEF. [Extracted from the article]

Abstract Background and objectives The literature about oral manifestations and dental management in maple syrup urine disease (MSUD) is sparse. The aim of this report is to present a new case of MSUD with special emphasis on oral findings and to review the relevant literature. Method A case report of a 4-year-old boy with MSUD was described according to the CARE guidelines for describing case reports. Scoping review of relevant literature was performed, according to the PRISMA-ScR guidelines, by searching PubMed, Medline, Embase, and the grey literature for articles describing dental management and/or oral manifestations in MSUD. Results The initial search identified 219 articles, but only 4 met the inclusion criteria. Rampant caries and plaque induced gingivitis were the main oro-dental findings in MSUD. Other oral findings included enamel hypoplasia, skeletal abnormalities, and abnormal oral behaviors. Disease-related factors appeared to play a major role in the development of the observed oral phenotype. Conclusion Oral health in MSUD seems to be influenced by the reliance on semi-synthetic diet and associated neurocognitive complications. Tailored oral health promotional interventions should be included in the multidisciplinary management of patients with MSUD.

ABSTRACTObjective The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km) time trial performance and blood electrolyte concentrations compared to a carbohydrate-electrolyte beverage (CE, GATORADE® Thirst Quencher) and distilled water (W).Methods During visit 1 (V1), participants (10 men and 10 women, 20–35 years old, BMI ≤ 29 kg/m2, recreationally active) reported to the laboratory whereby the following tests were performed: i) height and weight measurements, ii) body composition analysis, iii) treadmill testing to measure maximal aerobic capacity, and iv) 5-km time trial familiarization. The second visit (V2) was one week after V1 in the morning (0600 – 0900) and participants arrived 12–14 h fasted (no food or drink). The first battery of assessments (V2-T1) included nude body mass, urine specific gravity (USG), a profile of mood states (POMS) questionnaire, and the completion of a visual analogue scale (VAS) questionnaire to quantify cramping. Then heart rate (HR), blood pressure (BP), total body hydration (via bioelectrical impedance spectroscopy [BIS]) were examined. Finally, a measurement of blood markers via finger stick was performed. Participants consumed a randomized beverage (16 fl. oz. of MIDS, 16 fl. oz. of W, or 16 fl. oz. of CE) within 3 min followed by a 45-min rest. Following the rest period, a second battery (V2-T2) was performed whereby participants’ USG was assessed and they completed the POMS and VAS questionnaires, and HR, BP, and blood markers were measured. The participants then performed a 5-km treadmill time trial. Immediately following the 5-km time trial, participants completed a third testing battery (V2-T3) that began with blood markers, HR and BP assessments, followed by nude body weight assessment, and the POMS and VAS questionnaires. After 60 min, a fourth battery (V2-T4) was performed that included HR, BP, and blood markers. After sitting quietly for another 60 min a fifth battery assessment was performed (V2-T5) that included participants’ USG, POMS and VAS questionnaires, HR, BP, blood markers, and total body hydration. Visits 3 (V3) and 4 (V4) followed the same protocol except a different randomized drink (16 oz. of CE, MIDS, or W) was consumed; all of which were separated by approximately one week.Results No differences occurred between conditions for 5-km time trial completion, indirect calorimetry outcomes during 5-km time trials, USG, or nude mass measurements (p > 0.05 for all relevant statistical tests). However, blood potassium and the sodium/potassium ratio displayed significant interactions (p

Background and objectives: The literature about oral manifestations and dental management in maple syrup urine disease (MSUD) is sparse. The aim of this report is to present a new case of MSUD with special emphasis on oral findings and to review the relevant literature. Method: A case report of a 4-year-old boy with MSUD was described according to the CARE guidelines for describing case reports. Scoping review of relevant literature was performed, according to the PRISMA-ScR guidelines, by searching PubMed, Medline, Embase, and the grey literature for articles describing dental management and/or oral manifestations in MSUD. Results: The initial search identified 219 articles, but only 4 met the inclusion criteria. Rampant caries and plaque induced gingivitis were the main oro-dental findings in MSUD. Other oral findings included enamel hypoplasia, skeletal abnormalities, and abnormal oral behaviors. Disease-related factors appeared to play a major role in the development of the observed oral phenotype. Conclusion: Oral health in MSUD seems to be influenced by the reliance on semi-synthetic diet and associated neurocognitive complications. Tailored oral health promotional interventions should be included in the multidisciplinary management of patients with MSUD. [ABSTRACT FROM AUTHOR]

Metabolomics has been utilised in epidemiological studies to investigate biomarkers of nutritional status and metabolism in relation to non-communicable diseases. However, little is known about the effect of prandial status on several biomarker concentrations. Therefore, the aim of this intervention study was to investigate the effect of a standardised breakfast meal followed by food abstinence for 24 h on serum concentrations of amino acids, one-carbon metabolites and B-vitamin biomarkers. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20–30 years were served a breakfast meal (∼500 kcal) after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Circulating concentrations of most amino acids and metabolites linked to one-carbon metabolism peaked within the first 3 h after the meal. The branched-chain amino acids steadily increased from 6 or 8 hours after the meal, while proline decreased in the same period. Homocysteine and cysteine concentrations immediately decreased after the meal but steadily increased from 3 and 4 hours until 24 h. FMN and riboflavin fluctuated immediately after the meal but increased from 6 h, while folate increased immediately after the meal and remained elevated during the 24 h. Our findings indicate that accurate reporting of time since last meal is crucial when investigating concentrations of certain amino acids and one-carbon metabolites. Our results suggest a need for caution when interpretating studies, which utilise such biomarkers, but do not strictly control for time since the last meal. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) has reached epidemic proportions globally, including in Africa. However, molecular studies to understand the pathophysiology of T2D remain scarce outside Europe and North America. The aims of this study are to use an untargeted metabolomics approach to identify: (a) metabolites that are differentially expressed between individuals with and without T2D and (b) a metabolic signature associated with T2D in a population of Sub-Saharan Africa (SSA). Methods: A total of 580 adult Nigerians from the Africa America Diabetes Mellitus (AADM) study were studied. The discovery study included 310 individuals (210 without T2D, 100 with T2D). Metabolites in plasma were assessed by reverse phase, ultra-performance liquid chromatography and mass spectrometry (RP)/UPLC-MS/MS methods on the Metabolon Platform. Welch's two-sample t-test was used to identify differentially expressed metabolites (DEMs), followed by the construction of a biomarker panel using a random forest (RF) algorithm. The biomarker panel was evaluated in a replication sample of 270 individuals (110 without T2D and 160 with T2D) from the same study. Results: Untargeted metabolomic analyses revealed 280 DEMs between individuals with and without T2D. The DEMs predominantly belonged to the lipid (51%, 142/280), amino acid (21%, 59/280), xenobiotics (13%, 35/280), carbohydrate (4%, 10/280) and nucleotide (4%, 10/280) super pathways. At the sub-pathway level, glycolysis, free fatty acid, bile metabolism, and branched chain amino acid catabolism were altered in T2D individuals. A 10-metabolite biomarker panel including glucose, gluconate, mannose, mannonate, 1,5-anhydroglucitol, fructose, fructosyl-lysine, 1-carboxylethylleucine, metformin, and methyl-glucopyranoside predicted T2D with an area under the curve (AUC) of 0.924 (95% CI: 0.845–0.966) and a predicted accuracy of 89.3%. The panel was validated with a similar AUC (0.935, 95% CI 0.906–0.958) in the replication cohort. The 10 metabolites in the biomarker panel correlated significantly with several T2D-related glycemic indices, including Hba1C, insulin resistance (HOMA-IR), and diabetes duration. Conclusions: We demonstrate that metabolomic dysregulation associated with T2D in Nigerians affects multiple processes, including glycolysis, free fatty acid and bile metabolism, and branched chain amino acid catabolism. Our study replicated previous findings in other populations and identified a metabolic signature that could be used as a biomarker panel of T2D risk and glycemic control thus enhancing our knowledge of molecular pathophysiologic changes in T2D. The metabolomics dataset generated in this study represents an invaluable addition to publicly available multi-omics data on understudied African ancestry populations. [ABSTRACT FROM AUTHOR]

Herein we report the automation and scale-up of a photofluorination process key to the production of branched-chain aliphatic radiotracers such as (S)-5-[18F]fluorohomoleucine ((S)-5-[18F]]FHL). (S)-5-[18F]FHL is a leucine analogue that is primarily taken up by the L-type amino acid transporter (LAT or System L). LAT1 expression levels correlate closely with tumor proliferation, angiogenesis, and treatment outcomes, making it an attractive target for molecular imaging of cancer. We have previously synthesized (S)-5-[18F]FHL and tested this tracer in mice bearing PC3 (prostate) or U87 (glioma) xenografts in order to establish its feasibility for detecting and monitoring treatment for a broad range of cancers. In this study, the radiosynthesis of 5-[18F]FHL is demonstrated on an automated DT-PhotoFluor module with a radiochemical yield of 20.1 ± 4.8% (n = 3), radiochemical purity of 94.5 ± 4.9% (n = 3), and a synthesis time of ~ 75 min. The reported DT-PhotoFluor module will allow for higher molar activity, better reproducibility, and reduced radiation exposure for upcoming first-in-human studies. [ABSTRACT FROM AUTHOR]

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistance. HFD-fed Göttingen Minipig therefore represents a relevant animal model for studying host-microbiota interactions. No significant differences between the castrated and ovariectomized minipigs were observed. [ABSTRACT FROM AUTHOR]

Elevated levels of branched chain amino acids (BCAAs) and branched-chain α-ketoacids are associated with cardiovascular and metabolic disease, but the molecular mechanisms underlying a putative causal relationship remain unclear. The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid) is often used in preclinical models to increase BCAA oxidation and restore steady-state BCAA and branched-chain α-ketoacid levels. BT2 administration is protective in various rodent models of heart failure and metabolic disease, but confoundingly, targeted ablation of Bckdk in specific tissues does not reproduce the beneficial effects conferred by pharmacologic inhibition. Here, we demonstrate that BT2, a lipophilic weak acid, can act as a mitochondrial uncoupler. Measurements of oxygen consumption, mitochondrial membrane potential, and patch-clamp electrophysiology show that BT2 increases proton conductance across the mitochondrial inner membrane independently of its inhibitory effect on BCKDK. BT2 is roughly sixfold less potent than the prototypical uncoupler 2,4- dinitrophenol and phenocopies 2,4-dinitrophenol in lowering de novo lipogenesis and mitochondrial superoxide production. The data suggest that the therapeutic efficacy of BT2 may be attributable to the well-documented effects of mitochondrial uncoupling in alleviating cardiovascular and metabolic disease. [ABSTRACT FROM AUTHOR]

This article, titled "Low Arginine Suggesting the Diagnosis of Mitochondrial Cardiomyopathy," discusses the case of an 11-month-old male with developmental delay and failure to thrive who presented with severe dilated cardiomyopathy. The patient exhibited dysmorphic features and metabolic evaluation revealed low arginine levels, suggesting a mitochondrial disorder, specifically Barth syndrome. Further testing confirmed the diagnosis and treatment options, including arginine supplementation and elamipretide, were discussed. The article emphasizes the importance of early diagnosis and metabolic evaluation in patients with cardiomyopathies and highlights the characteristic features and biochemical abnormalities associated with Barth syndrome. [Extracted from the article]

The Entner–Doudoroff (ED) pathway provides an alternative to glycolysis. It converts 6-phosphogluconate (6-PG) to glyceraldehyde-3-phosphate and pyruvate in two steps consisting of a dehydratase (EDD) and an aldolase (EDA). Here, we investigate its distribution and significance in higher plants and determine the ED pathway is restricted to prokaryotes due to the absence of EDD genes in eukaryotes. EDDs share a common origin with dihydroxy-acid dehydratases (DHADs) of the branched chain amino acid pathway (BCAA). Each dehydratase features strict substrate specificity. E. coli EDD dehydrates 6-PG to 2-keto-3-deoxy-6-phosphogluconate, while DHAD only dehydrates substrates from the BCAA pathway. Structural modeling identifies two divergent domains which account for their non-overlapping substrate affinities. Coupled enzyme assays confirm only EDD participates in the ED pathway. Plastid ancestors lacked EDD but transferred metabolically promiscuous EDA, which explains the absence of the ED pathway from the Viridiplantae and sporadic persistence of EDA genes across the plant kingdom. The Enter-Doudoroff (ED) pathway is an alternative to glycolysis present in some prokaryotes. Evans et al. show that its dehydratase enzyme, evolved from a branched chain amino acid pathway paralog, acquired a new function through mutations in its active site. [ABSTRACT FROM AUTHOR]

Silk gland size in silkworms (Bombyx mori) affects silk output. However, the molecular mechanisms by which genes regulate silk gland size remain unclear. In this study, silk glands from three pure silkworm strains (A798, A306 and XH) with different silk gland weight phenotypes were compared using transcriptomics and proteomics to identify differentially expressed genes (DEGs) and proteins (DEPs). When comparing A798 to A306 and A798 to XH, 830 and 469 DEGs were up‐regulated, respectively. These genes were related to the gene ontology terms, metabolic process, transport activity and biosynthesis process. In addition, 372 and 302 up‐regulated differentially expressed proteins were detected in A798 to A306 and A798 to XH, respectively, related to the gene ontology terms, ribosome and protein export, ribosome and polypeptide biosynthesis processes. Moreover, combined transcriptomics, proteomics and weighted correlation network analyses showed that five genes (BGIBMGA002524, BGIBMGA002629, BGIBMGA005659, BGIBMGA005711 and BGIBMGA010889) were significantly associated with the silk gland weight. Reverse Transcription‐quantitative real‐time Polymerase Chain Reaction (RT‐qPCR) and Enzyme linked immunosorbent assay (ELISA) were used to verify the mRNA and protein expression of five genes in the silk glands and tissues of 18 silkworm strains. The results showed that four genes have higher expression levels in heavier silk glands. These genes are associated with glycogen metabolism, fatty acid synthesis and branched chain amino acid metabolism, thus potentially promoting growth and silk protein synthesis. These findings provide valuable insights into the molecular mechanisms underlying the relationship between silk gland weight and silk yield in silkworms. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the association of dietary branched-chain amino acids (BCAAs) and its components with cancer, cancer mortality, and all-cause mortality in a meta-analysis of observational studies. A comprehensive search was conducted between electronic databases (PubMed, Scopus, and Web of Science) until September 2022. Odds ratios (OR), hazard ratios (HR), and relative risks (RR) were extracted. Eight articles (six studies on breast cancer (BC) and digestive cancers risk, and three studies on both BC and digestive cancers mortality, and all-cause mortality) were included. The present study showed no statistically significant association between dietary BCAAs and its components with BC and digestive cancers (RRBCAA: 0.87, 95% CI: 0.68–1.10, RRLeucine: 0.74, 95% CI: 0.52–1.04, RRIsoleucine: 0.98, 95% CI: 0.93–1.04, RRValine: 0.76, 95% CI: 0.55–1.05). Also, no statistically significant relationship between dietary BCAAs and its components with both BC and digestive cancers mortality (RRBCAA: 0.95, 95% CI: 0.68–1.33, RRLeucine: 0.95, 95% CI: 0.79-1.15, RRIsoleucine: 0.95, 95% CI: 0.79–1.14, RRValine: 1.01, 95% CI: 0.84–1.21) and all-cause mortality (RRBCAA: 0.98, 95% CI: 0.73–1.32, RRLeucine: 1.02, 95% CI: 0.81–1.29, RRIsoleucine: 0.96, 95% CI: 0.73–1.27, RRValine: 1.02, 95% CI: 0.79–1.32) were observed. Our findings showed no significant association between dietary BCAAs and its components with BC and digestive cancers, BC and digestive cancers mortality, and all-cause mortality. [ABSTRACT FROM AUTHOR]

Purpose of the study: Breast density is an established risk factor for breast cancer. However, little is known about metabolic influences on breast density phenotypes. We conducted untargeted serum metabolomics analyses to identify metabolic signatures associated with breast density phenotypes among young women. Methods: In a cross-sectional study of 173 young women aged 25–29 who participated in the Dietary Intervention Study in Children 2006 Follow-up Study, 449 metabolites were measured in fasting serum samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable-adjusted mixed-effects linear regression identified metabolites associated with magnetic resonance imaging measured breast density phenotypes: percent dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute non-dense breast volume (ANDBV). Metabolite results were corrected for multiple comparisons using a false discovery rate adjusted p-value (q). Results: The amino acids valine and leucine were significantly inversely associated with %DBV. For each 1 SD increase in valine and leucine, %DBV decreased by 20.9% (q = 0.02) and 18.4% (q = 0.04), respectively. ANDBV was significantly positively associated with 16 lipid and one amino acid metabolites, whereas no metabolites were associated with ADBV. Metabolite set enrichment analysis also revealed associations of distinct metabolic signatures with %DBV, ADBV, and ANDBV; branched chain amino acids had the strongest inverse association with %DBV (p = 0.002); whereas, diacylglycerols and phospholipids were positively associated with ANDBV (p ≤ 0.002), no significant associations were observed for ADBV. Conclusion: Our results suggest an inverse association of branched chain amino acids with %DBV. Larger studies in diverse populations are needed. [ABSTRACT FROM AUTHOR]

The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention. [ABSTRACT FROM AUTHOR]

The branched-chain amino acid (BCAA) is a group of essential amino acids that are involved in maintaining the energy balance of a human being as well as the homoeostasis of GABAergic, glutamatergic, serotonergic and dopaminergic systems. Disruption of these systems has been associated with the pathophysiology of autism while low levels of these amino acids have been discovered in patients with autism. A pilot open-label, prospective, follow-up study of the use of BCAA in children with autistic behaviour was carried out. Fifty-five children between the ages of 6 and 18 participated in the study from May 2015 to May 2018. We used a carbohydrate-free BCAA-powdered mixture containing 45·5 g of leucine, 30 g of isoleucine and 24·5 g of valine in a daily dose of 0·4 g/kg of body weight which was administered every morning. Following the initiation of BCAA administration, children were submitted to a monthly psychological examination. Beyond the 4-week mark, BCAA were given to thirty-two people (58·18 %). Six of them (10·9 %) discontinued after 4–10 weeks owing to lack of improvement. The remaining twenty-six children (47·27 %) who took BCAA for longer than 10 weeks displayed improved social behaviour and interactions, as well as improvements in their speech, cooperation, stereotypy and, principally, their hyperactivity. There were no adverse reactions reported during the course of the treatment. Although these data are preliminary, there is some evidence that BCAA could be used as adjunctive treatment to conventional therapeutic methods for the management of autism. [ABSTRACT FROM AUTHOR]

Flag leaf, stem, and grain are all important for endosperm development (grain filling) in cereal crops. However, joint analysis of these three tissues during grain filling is limited. Hence, we employed RNA‐seq to compare the transcription dynamics in flag leaf, stem, and grain at different stages during grain filling. The differentially expressed genes (DEGs) between different tissues and stages were identified. The number of DEGs was increased from stage 2 to stage 4 in leaf and grain, while the number of DEGs was decreased in the stem. Through WGCNA analysis, genes associated with photosynthesis were specifically changed in flag leaves during grain filling. Lignin and branched chain amino acid synthesis‐related genes were specifically expressed in stem and grain, respectively. The phytohormone signal transduction and sucrose‐starch conversion pathway in stem and grain together promoted the offloading of assimilates from stem to grain and the assimilate accumulation in grain. These results provide new insights for further investigations on molecular regulatory mechanisms among different tissues of grain filling, and also provide a new idea for improvement of yield and quality in cereal crops. [ABSTRACT FROM AUTHOR]