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Staphylococcus aureus is a Gram-positive, opportunistic human pathogen that is a leading cause of skin and soft tissue infections and invasive disease worldwide. Virulence in this bacterium is tightly controlled by a network of regulatory factors. One such factor is the global regulatory protein CodY. CodY links branched-chain amino acid sufficiency to the production of surface-associated and secreted factors that facilitate immune evasion and subversion. Our previous work revealed that CodY regulates virulence factor gene expression indirectly in part by controlling the activity of the SaeRS two-component system (TCS). While this is correlated with an increase in membrane anteiso-15:0 and -17:0 branched-chain fatty acids (BCFAs) derived from isoleucine, the true mechanism of control has remained elusive. Herein, we report that CodY-dependent regulation of SaeS sensor kinase activity requires BCFA synthesis. During periods of nutrient sufficiency, BCFA synthesis and Sae TCS activity are kept relatively low by CodY-dependent repression of the ilv-leu operon and the isoleucine-specific permease gene brnQ2 . In a codY null mutant, which simulates extreme nutrient limitation, de-repression of ilv-leu and brnQ2 directs the synthesis of enzymes in redundant de novo and import pathways to upregulate production of BCFA precursors. Overexpression of brnQ2, independent of CodY, is sufficient to increase membrane anteiso BCFAs, Sae-dependent promoter activity, and SaeR ~ P levels. Our results further clarify the molecular mechanisms by which CodY controls virulence in S. aureus .IMPORTANCEExpression of bacterial virulence genes often correlates with the exhaustion of nutrients, but how the signaling of nutrient availability and the resulting physiological responses are coordinated is unclear. In S. aureus, CodY controls the activity of two major regulators of virulence-the Agr and Sae two-component systems (TCSs)-by unknown mechanisms. This work identifies a mechanism by which CodY controls the activity of the sensor kinase SaeS by modulating the levels of anteiso branched-chain amino acids that are incorporated into the membrane. Understanding the mechanism adds to our understanding of how bacterial physiology and metabolism are linked to virulence and underscores the role virulence in maintaining homeostasis. Understanding the mechanism also opens potential avenues for targeted therapeutic strategies against S. aureus infections., Competing Interests: The authors declare no conflict of interest.

Introduction: Emerging evidences suggests that the disrupted branched-chain amino acids (BCAAs) homeostasis and elevated BCAAs promote obesity-related insulin resistance (IR). Exercise improves insulin sensitivity. However, whether BCAAs plays a role in the exercise-attenuated IR remains to be fully investigated., Methods: In this study, male C57BL/6J mice were induced to become diet-induced obese (DIO) and served as subjects. The initial investigation focused on the impact of exercise on IR and BCAAs. The DIO mice were randomly assigned to either a sedentary group (CON, n  = 16) or an exercise group (EX, n  = 16). The EX group underwent a 12-week aerobic exercise regimen on a treadmill. After 12-week, plasma BCAAs and branched-chain keto acids (BCKAs) were measured by liquid chromatography-mass spectrometry, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the expression and phosphorylation of BCAAs catabolic proteins, as well as AKT T308 in gastrocnemius muscle and liver tissues, were evaluated using western blotting. Subsequently, the study explored the role of BCAAs in enhancing IR through exercise. Mice were randomly allocated into 4 groups: sedentary group (CON, n  = 8), sedentary with BCAAs supplementation group (CON+BCAA, n  = 8), exercise group (EX, n  = 16), and exercise with BCAAs supplementation group (EX+BCAA, n  = 16). The exercise protocol was as above. Mice in the BCAAs supplemented groups received drinking water containing 2% BCAAs. After 12-week, plasma BCAAs and BCKAs were measured, GTT and ITT tests were performed, and the phosphorylation of AKT T308, as well as p70S6K T389 in gastrocnemius muscle and liver, were compared between the EX group and the EX+BCAA group. Additionally, the phosphorylation of AMPKα T172 in both tissues was measured across all four groups., Results: 12-week aerobic exercise improved insulin sensitivity in DIO mice while inducing BCAAs catabolic protein expression in skeletal muscle and liver, and reducing the plasma BCAAs level. Importantly, BCAAs supplementation elevated the plasma level of BCAAs and counteracted the exercise-attenuated IR. In skeletal muscle and liver tissues, BCAAs supplementation impaired the exercise-improved insulin signaling without enhancing mammalian target of rapamycin activity. AMPK activity was enhanced by aerobic exercise, which was abolished by BCAAs supplementation., Conclusion: Aerobic exercise attenuated insulin resistance via restoring BCAAs homeostasis and AMPK activity. The impacts of BCAAs intake on the metabolic effects of exercise sheds light on the combined exercise and nutrition intervention strategy for diabetes management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Liu, Wei, Dong, Sun, Zhang and Qiu.)

Brown and beige adipocytes utilize a variety of substrates for cold-induced thermogenesis, contributing to the clearance of metabolites in circulation and, consequently, metabolic health. Food-derived compounds that exhibit agonistic activity at temperature-sensitive transient receptor potential channels may serve as cold mimics to elicit thermogenesis and substrate utilization in brown adipose tissue (BAT). In addition to fatty acids and glucose, branched-chain amino acids (BCAAs), which are essential amino acids obtained from foods, are actively catabolized in BAT through mitochondrial BCAA carrier (MBC). The relative contribution of BCAAs to fueling the tricarboxylic acid cycle as a substrate (i.e., anaplerosis) is estimated to be relatively small, yet BCAA catabolism in BAT exerts a critical role in systemic insulin sensitivity. The nature of this apparent tension remained unclear until the recent discovery that active BCAA catabolism in BAT through MBC is critical for the synthesis of metabolites such as glutathione, which is delivered to the liver to improve hepatic insulin sensitivity through redox homeostasis. Novel mechanistic insights into the control of BAT function and systemic metabolism reveal the therapeutic potential of food-derived compounds for improving metabolic flexibility and insulin sensitivity.

For vegetarians or vegan athletes, improving the utilization of plant-based protein and the absorption of amino acids is crucial. This study explored the impact of combining pea protein with Lactiplantibacillus plantarum TWK10 and resistance training on amino acid absorption and exercise performance. Sixteen male and sixteen female participants were randomly assigned to either a control group (20 g of pea protein without TWK10) or a TWK10 group (20 g of pea protein combined with 1 × 10 10  colony-forming units of TWK10). After 28 days of supplementation combined with resistance exercise training three times per week. All subjects underwent body composition and muscle strength performance, plasma and fecal samples were collected for microbiota analysis and blood amino acid concentrations. The TWK10 group showed a significant increase in muscle thickness and improvements were observed in 1 repetition maximum bench press, explosive, anaerobic power output compared to before the intervention, and were significantly higher than those in the control group ( p  < 0.05). TWK10 supplementation significantly increased the area under the curve and maximum concentration of branched-chain amino acids, essential amino acids, and total amino acids ( p  < 0.05). Furthermore, TWK10 supplementation effectively increased the richness of gut bacterial families. Our study demonstrated that the TWK10 significant increase in the abundance of specific bacterial families in the gut, resulting in increased pea protein amino acid absorption. Moreover, increasing muscle mass and significantly improving muscle thickness, muscle strength, power, and anaerobic capacity., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yi-Chu Liao reports a relationship with Culture Collection & Research Institute, SYNBIO TECH INC that includes: employment. Yi-Chen Cheng reports a relationship with Culture Collection & Research Institute, SYNBIO TECH INC that includes: employment. Chia-Chia Lee reports a relationship with Culture Collection & Research Institute, SYNBIO TECH INC that includes: employment. Jin-Seng Lin reports a relationship with Culture Collection & Research Institute, SYNBIO TECH INC that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The adverse metabolic impacts of branched-chain amino acids (BCAA) have been elucidated are mediated by isoleucine and valine. Dietary restriction of isoleucine promotes metabolic health and increases lifespan. However, a high protein diet enriched in BCAA is presently the most useful therapeutic strategy for nonalcoholic fatty liver disease (NAFLD), yet, its underlying mechanism remains largely unknown. Fatty liver hemorrhagic syndrome (FLHS), a specialized laying hen NAFLD model, can spontaneously develop fatty liver and hepatic steatosis under a high-energy and high-protein dietary background that the pathogenesis of FLHS is similar to human NAFLD. The mechanism underlying dietary BCAA control of NAFLD development in laying hens remains unclear. Herein, we demonstrate that dietary supplementation with 67 % High BCAA has unique mitigative impacts on NAFLD in laying hens. A High BCAA diet alleviates NAFLD, by inhibiting the tryptophan-ILA-AHR axis and MAPK9-mediated de novo lipogenesis (DNL), promoting ketogenesis and energy metabolism, and activating PPAR-RXR and pexophagy to promote fatty acid β-oxidation. Furthermore, we uncover that High BCAA strongly activates ubiquitin-proteasome autophagy via downregulating UFMylation to trigger MAPK9-mediated DNL, fatty acid elongation and lipid droplet formation-related proteins ubiquitination degradation, activating PPAR-RXR and pexophagy mediated fatty acid β-oxidation and lipolysis. Together, our data highlight moderating intake of high BCAA by inhibiting the AHR/MAPK9 are promising new strategies in NAFLD and FLHS treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ovarian cancer is the sixth leading cause of cancer-related mortality among individuals with ovaries, and high-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype. Characterized by a distinct and aggressive metastatic pattern, HGSOC can originate in the fallopian tube with the transformation of fallopian tube epithelial (FTE) cells, which metastasize to the ovary and subsequently to the omentum and peritoneal cavity. The omentum is a privileged metastatic site, and the metabolic exchange underlying omental metastasis could provide enzyme or receptor targets to block spread. In this study, we adapted a mass spectrometry imaging (MSI) protocol to investigate spatial location of 3D cocultures of tumorigenic FTE cells when grown in proximity to murine omental explants as a model of early metastatic colonization. Our analysis revealed several altered metabolites in tumorigenic FTE/omentum cocultures, namely changes in branched-chain amino acids (BCAA), including valine. We quantified the heightened consumption of valine, other BCAAs, and other amino acid-derived metabolites in omental cocultures using LC-MS assays. Our analysis revealed that metabolite concentrations when monitored with MSI from cell culture media in living culture systems have notable considerations for how MSI data may produce signatures that induce ionization suppression. Supplementation with valine enhanced proliferation and mTOR signaling in tumorigenic FTE cells, suggesting the potential of BCAA's as a nutrient utilized by tumor cells during omental colonization and a possible target for metastasis.

Plasma levels of branched-chain amino acids (BCAA) and their metabolites, branched-chain ketoacids (BCKA), are increased in insulin resistance. We previously showed that ketoisocaproic acid (KIC) suppressed insulin-stimulated glucose transport in L6 myotubes, especially in myotubes depleted of branched-chain ketoacid dehydrogenase (BCKD), the enzyme that decarboxylates BCKA. This suggests that upregulating BCKD activity might improve insulin sensitivity. We hypothesised that increasing BCAA catabolism would upregulate insulin-stimulated glucose transport and attenuate insulin resistance induced by BCKA. L6 myotubes were either depleted of BCKD kinase (BDK), the enzyme that inhibits BCKD activity, or treated with BT2, a BDK inhibitor. Myotubes were then treated with KIC (200 μM), leucine (150 μM), BCKA (200 μM), or BCAA (400 μM) and then treated with or without insulin (100 nM). BDK depletion/inhibition rescued the suppression of insulin-stimulated glucose transport by KIC/BCKA. This was consistent with the attenuation of IRS-1 (Ser612) and S6K1 (Thr389) phosphorylation but there was no effect on Akt (Ser473) phosphorylation. The effect of leucine or BCAA on these measures was not as pronounced and BT2 did not influence the effect. Induction of the mTORC1/IRS-1 (Ser612) axis abolished the attenuating effect of BT2 treatment on glucose transport in cells treated with KIC. Surprisingly, rapamycin co-treatment with BT2 and KIC further reduced glucose transport. Our data suggests that the suppression of insulin-stimulated glucose transport by KIC/BCKA in muscle is mediated by mTORC1/S6K1 signalling. This was attenuated by upregulating BCAA catabolic flux. Thus, interventions targeting BCAA metabolism may provide benefits against insulin resistance and its sequelae., Competing Interests: The authors declare none., (© The Author(s) 2024.)

Background: Metabolic syndrome (MetS) is identified by the manifestation of a minimum of three out of five metabolic abnormalities, including insulin resistance, hypertension, hypertriglyceridemia, abdominal obesity, and low levels of high-density lipoprotein cholesterol. The present study aimed to assess the association between dietary branched-chain amino acids (BCAA) intakes and MetS, due to available conflicting evidence., Methods: A total of 4,860 individuals who had participated in the baseline phase of the PERSIAN (Prospective Epidemiological Research Studies in IrAN) Kavar cohort study were included in our study. The daily intake of valine, leucine, and isoleucine were evaluated using a semi-quantitative food frequency questionnaire. The association between dietary BCAA intake with MetS and its components was evaluated using logistic regression analysis., Results: The mean intake of BCAA among the included subjects was 7.65 (standard deviation [SD]: 2.92), and the prevalence of MetS was found to be 49.2%. Multivariable logistic regression analysis revealed an inverse association between 1-S.D. increment in dietary valine (odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.78-0.94), leucine (OR = 0.85, 95% CI: 0.77-0.93), isoleucine (OR = 0.84, 95% CI: 0.76-0.93), and total BCAA (OR = 0.85, 95% CI: 0.77-0.93) intake and the odds of MetS. There were also a significant association between BCAA intakes and hyperglycemia and hypertriglyceridemia., Conclusion: We observed a significant inverse association between dietary BCAA intake and MetS, hyperglycemia, and hypertriglyceridemia, regardless of confounding factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shojaei-Zarghani, Fattahi, Mansourabadi and Safarpour.)

Three hundred and sixty sows were used to investigate the effect of various dietary branched-chain amino acids (BCAA) levels on sow lactation and piglet growth performance. On day 112 ± 1.4 of gestation, sows were blocked by the parity group (P1, P2, P3+) and randomly assigned to 1 of 6 dietary treatments containing various levels of standardized ileal digestible (SID) Leu, Ile, and Val. The experimental diets were formulated to the desired levels of BCAA by replacing cornstarch in a basal diet with l-leucine, l-isoleucine, and l-valine. Dietary BCAA levels relative to SID Lys were 114% or 180% for Leu, 56% or 64% for Ile, and 64% or 120% for Val. Diets were formulated to be isocaloric (3.23 Mcal ME/kg) and met or exceeded all other NRC (2012) essential amino acid and vitamin and mineral recommendations. Sow body weight (BW) and backfat thickness were measured at the time of entry into the farrowing room and at weaning. Piglet litter weights were recorded after cross-fostering and weaning to calculate the litter growth rate. Data were analyzed using generalized linear mixed models with fixed effects of dietary treatment and parity group and a random effect of lactation group. The models were fit using R (v4.4.1; R Core Team, 2024). The sow and her litter were the experimental unit, and results were considered significant if P  < 0.05. On average, sows nursed their litters for 21.3 d ( P  = 0.998). The mean parity by treatment ranged from 3.8 to 3.9 ( P  = 0.999). After farrowing, the mean sow BW was 220 kg with a range between treatments of 216 to 222 kg ( P  = 0.523). On average, sows gained 2.3% of their BW ( P  = 0.740) with an average daily feed intake of 8.74 kg/d ( P  = 0.903). As expected, sow Leu, Ile, and Val intakes were different across treatments ( P  ≤ 0.001) and corresponded to the varying dietary levels of BCAA. Sows entered farrowing with an average backfat thickness of 11.50 mm ( P  = 0.919) and lost 6.5% backfat through lactation ( P  = 0.880). Sows started the trial with an average of 14.1 piglets/sow ( P  = 0.967) and weaned 12.7 piglets/sow ( P  = 0.995) with a piglet ADG of 0.22 kg/d ( P  = 0.280) and a daily litter growth rate of 2.90 kg/d ( P  = 0.547). In conclusion, there was no evidence of an effect of the various leucine, isoleucine, and valine levels evaluated in this study on lactating sow and piglet performance., Competing Interests: Keith Haydon is an employee of CJ America—Bio. CJ America—Bio provided financial support for this project., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Abstract Background Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. Methods Seventy-eight outpatients with moderate to severe COPD (GOLD II–IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC–MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. ɑ

Muscle inactivity leads to muscle atrophy. Leucine is known to inhibit protein degradation and to promote protein synthesis in skeletal muscle. We tested the ability of a high-protein diet enriched with branched-chain amino acids (BCAAs) to prevent muscle atrophy during long-term bed rest (BR). We determined body composition (using dual energy x-ray absorptiometry) at baseline and every 2-weeks during 60 days of BR in 16 healthy young women. Nitrogen (N) balance was assessed daily as the difference between N intake and N urinary excretion. The subjects were randomized into two groups: one received a conventional diet (1.1 ± 0.03 g protein/kg, 4.9 ± 0.3 g leucine per day) and the other a high protein, BCAA-enriched regimen (1.6 ± 0.03 g protein-amino acid/kg, 11.4 ± 0.6 g leucine per day). There were significant BR and BR × diet interaction effects on changes in lean body mass (LBM) and N balance throughout the experimental period (repeated measures ANCOVA). During the first 15 days of BR, lean mass decreased by 4.1 ± 0.9 and 2.4 ± 2.1% (p < 0.05) in the conventional and high protein-BCAA diet groups, respectively, while at the end of the 60-day BR, LBM decreased similarly in the two groups by 7.4 ± 0.7 and 6.8 ± 2.4%. During the first 15 days of BR, mean N balance was 2.5 times greater (p < 0.05) in subjects on the high protein-BCAA diet than in those on the conventional diet, while we did not find significant differences during the following time intervals. In conclusion, during 60 days of BR in females, a high protein-BCAA diet was associated with an early protein-LBM sparing effect, which ceased in the medium and long term.

BackgroundPrevious studies showed conflicting evidence on the association between the intake of dietary branched-chain amino acid (BCAA) and the risk of cardiovascular disease (CVD). However, this relationship has not been studied in patients with type 2 diabetes. Therefore, we evaluated the effects of total and individual dietary BCAA (leucine, isoleucine, and valine) intake on CVD risk among individuals with type 2 diabetes in China.Materials and methodsA total of 419 patients with type 2 diabetes who have been diagnosed with CVD (within 2 weeks) were recruited between March 2013 and September 2015 in China. Cases with CVD were 1:1 matched to controls with type 2 diabetes but without CVD by age (±5 years) and sex. A validated 79-item semiquantitative food frequency questionnaire (FFQ) was administered to assess the participants' dietary data. Total dietary BCAA per individual was the summation of the daily intake of isoleucine, leucine, and valine. OR and corresponding CIs were computed by conditional logistic regression models adjusted for potential confounders.ResultsMedian values of the daily intake of total BCAA were 11.87 g, with an interquartile range of 10.46–13.15 g for cases, and 12.47 g, with an interquartile range of 11.08–13.79 g for controls (P = 0.001). Dietary BCAA was inversely related to CVD risk after multivariable adjustment (OR Q4−Q1 = 0.23, 95%CI = 0.10, 0.51, P trend

This study aimed to characterize dietary protein patterns (DPPs) in a sample pool of 298 well-nourished pregnant women and explore potential associations between DPPs and neonatal anthropometrics. Maternal dietary data were collected using a validated food frequency questionnaire. Neonatal anthropometrics were abstracted from health booklets. A hierarchical cluster analysis identified three DPPs: “Dairy-focused”, “Med-fusion”, and “Traditional-inspired”. The “Dairy-focused” DPP exhibited the highest protein intake (p < 0.001), predominantly animal protein (p < 0.001), while the “Traditional-inspired” DPP presented higher plant protein (p < 0.001) and fiber intakes (p < 0.001), and, therefore, a reduced carbohydrate-to-fiber quotient (p < 0.001). The “Med-fusion” DPP had the lowest protein-to-fat ratio (p < 0.001). Infants of women following the “Dairy-focused” DPP had the highest birth height centiles (p = 0.007) and the lowest ponderal index (p = 0.003). The NMR-metabolomics approach was implemented on a subset of women that provided amniotic fluid (AF) specimens (n = 62) to elucidate distinct metabolic signatures associated with DPPs. PCA and OPLS-DA models verified the adherence to three DPPs, revealing that the levels of several amino acids (AAs) were the highest in “Dairy-focused”, reflecting its protein-rich nature. The “Traditional-inspired” DPP showed decreased AAs and glucose levels. This knowledge may contribute to optimizing maternal dietary recommendations. Further research is needed to validate these findings and better understand the relationships between maternal diet, AF metabolic signature, and neonatal anthropometrics.

Summary: Ultrasound‐assisted alkaline extraction (UAAE) and the nutritional quality of proteins from five algae (Arthrospira platensis, Cladophora glomerata, Porphyra tenera, Laminaria japonica and Undaria pinnatifida) were investigated. The UAAE of the A. platensis protein using a 60% amplitude level and 30 min extraction time provided the highest protein yield (81.86%) and altered the surface of A. platensis. Amino acid profiles revealed that lysine and branched‐chain amino acids (BCAAs) were dominant in most algal proteins. The C. glomerata protein had the highest digestibility (94.09%) and protein digestibility‐corrected amino acid scores for the BCAAs. The L. japonica protein demonstrated a rich source of aspartic and glutamic acids, giving an umami taste. The algal proteins contained low contents of carbohydrates (3.87–44.83 mg glucose equivalents g−1) and nucleic acids (0.60–8.57 mg g−1), while total phenolics were 6.13–70.13 mg gallic acid equivalents g−1. Algal proteins could be a good ingredient in developing vegan and vegetarian foods. [ABSTRACT FROM AUTHOR]

Background and Objectives: Vitamin D is involved in pancreatic beta-cell function, insulin sensitivity, and inflammation. Further, elevation in branched-chain amino acids (BCAAs) has been implicated in type 2 diabetes (T2DM) pathology. However, the relationship between vitamin D and BCAAs in T2DM remains unclear. The current study aimed to investigate the relationship between vitamin D and BCAAs in T2DM. Materials and Methods: In total, 230 participants (137 with T2DM and 93 healthy controls) were recruited in a cross-sectional study. Furthermore, an additional follow-up study was performed, including 20 T2DM patients with vitamin D deficiency. These patients were prescribed weekly vitamin D tablets (50,000 IU) for three months. The levels of several biochemical parameters were examined at the end of the vitamin D supplementation. Results: The results showed that patients with T2DM had higher serum levels of BCAAs and lower serum levels of 25-hydroxyvitamin D (25(OH)D) compared with those of the healthy controls (p < 0.01). The serum levels of vitamin D were negatively correlated with BCAA levels in T2DM patients (r = −0.1731, p < 0.05). In the follow-up study, 25(OH)D levels were significantly improved (p < 0.001) following vitamin D supplementation. Vitamin D supplementation significantly reduced the levels of BCAAs, HbA1c, total cholesterol, triglycerides, and fasting glucose (p < 0.01). Conclusion: Overall, these results suggest a role for BCAAs and vitamin D in the etiology and progression of T2DM. Thus, managing vitamin D deficiency in patients with T2DM may improve glycemic control and lower BCAA levels. [ABSTRACT FROM AUTHOR]

There is a lack of evidence on the impact on body composition of high protein intake and types of protein substitutes in PKU patients—particularly in adolescents, who are more inclined to dietary transgressions. In this observational, cross-sectional study, PKU patients were observed during prepubertal age (p) or after the pubertal spurt (P), assessing body composition and bone quality and correlating these parameters with dietary compliance and types of protein substitutes. Anthropometric and dietary data were evaluated together with bioelectrical impedance analysis (BIA), quantitative ultrasound (QUS) and branched-chain amino acids (BCAAs). A total of 36 patients (16 males, 17 prepubertal and 19 post-pubertal; mean ± SD age 11.4 ± 3.9 years) were included. A higher BMI was observed in adolescents (p-value: 0.018). The BIA revealed a significant increase in total body water (TBW) and muscle mass (MM) in P subjects either compliant (p-value: 0.001) or non-compliant with the diet (p-value: 0.001). MM content correlated with increased Phe intake (r = 0.63; p < 0.001). In the subgroup of five patients taking L-AAs and glycomacropeptides (GMPs), BCAA values tended to be lower than those taking only L-AA mixtures, with a significant trend for valine. Maintenance of body composition parameters within the normal range—for both fat and muscle mass—and levels of BCAAs can be helpful in reducing the risk of becoming overweight in adulthood. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Circulating levels of acylcarnitines (ACs) have been associated with the risk of various diseases such as cancer and type 2 diabetes. Diet and lifestyle factors have been shown to influence AC concentrations but a better understanding of their biological, lifestyle and metabolic determinants is needed. Circulating ACs were measured in blood by targeted (15 ACs) and untargeted metabolomics (50 ACs) in 7770 and 395 healthy participants of the European Prospective Investigation into Cancer and Nutrition (EPIC), respectively. Associations with biological and lifestyle characteristics, dietary patterns, self-reported intake of individual foods, estimated intake of carnitine and fatty acids, and fatty acids in plasma phospholipid fraction and amino acids in blood were assessed. Age, sex and fasting status were associated with the largest proportion of AC variability (partial-r up to 0.19, 0.18 and 0.16, respectively). Some AC species of medium or long-chain fatty acid moiety were associated with the corresponding fatty acids in plasma (partial-r = 0.24) or with intake of specific foods such as dairy foods containing the same fatty acid. ACs of short-chain fatty acid moiety (propionylcarnitine and valerylcarnitine) were moderately associated with concentrations of branched-chain amino acids (partial-r = 0.5). Intake of most other foods and of carnitine showed little association with AC levels. Our results show that determinants of ACs in blood vary according to their fatty acid moiety, and that their concentrations are related to age, sex, diet, and fasting status. Knowledge on their potential determinants may help interpret associations of ACs with disease risk and inform on potential dietary and lifestyle factors that might be modified for disease prevention. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common, heterogeneous endocrine disorder which effects 5-10% of reproductive-age women. Recently, an association between PCOS and an increased risk of developing metabolic disturbances, such as insulin resistance, prediabetes, type 2 diabetes mellitus as well as obesity has been emphasised. Branched-chain amino acids (BCAAs), including valine (Val), leucine (Leu) and isoleucine (Ile), are a group of essential amino acids that cannot be synthesized in human body and need to be obtained from food. Several recent studies provide evidence that plasma BCAAs also serve as crucial nutrient signals and metabolic regulators. Interestingly, latest metabolomics analysis shows abnormalities in amino acid catabolism and biosynthesis in patients with PCOS, particularly in BCAAs. A growing body of evidence proves that elevated levels of BCAAs may have adverse effects on metabolic health leading to the development of insulin resistance, prediabetes, type 2 diabetes mellitus and obesity both in human and animal models. The aim of this review is to assess the current state of knowledge about the potential role of BCAAs as a novel biomarker of metabolic disturbances in women with polycystic ovary syndrome based on recent scientific literature published up to July 2021 and searches of the PubMed, Google Scholar, and Web of Science databases. [ABSTRACT FROM AUTHOR]

Branched-chain amino acids (BCAAs), essential amino acids for the human body, are mainly obtained from food. High levels of BCAAs in circulation are considered as potential markers of metabolic-associated fatty liver disease (MAFLD) in humans. However, there are conflicting reports about the effects of supplement of BCAAs on MAFLD, and research on BCAAs and gut microbiota is not comprehensive. Here, C57BL/6J mice were fed with a high-fat diet with or without BCAAs to elucidate the effects of BCAAs on the gut microbiota and metabolic functions in a mouse model of MAFLD. Compared to high-fat diet (HFD) feeding, BCAA supplementation significantly reduced the mouse body weight, ratio of liver/body weight, hepatic lipid accumulation, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT), and the expressions of the lipogenesis-related enzymes Fas, Acc, and Scd-1 and increased expressions of the lipolysis-related enzymes Cpt1A and Atgl in the liver. BCAAs supplementation also counteracted HFD-induced elevations in serum BCAAs levels by stimulating the enzymatic activity of BCKDH. Furthermore, BCAAs supplementation markedly improved the gut bacterial diversity and altered the gut microbiota composition and abundances, especially those of genera, in association with MAFLD and BCAAs metabolism. These data suggest that BCAA treatment improves HFD-induced MAFLD through mechanisms involving intestinal microbes. [ABSTRACT FROM AUTHOR]

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI. [ABSTRACT FROM AUTHOR]

Initial military training (IMT) results in increased fat‐free mass (FFM) and decreased fat mass (FM). The underlying metabolic adaptations facilitating changes in body composition during IMT are unknown. The objective of this study was to assess changes in body composition and the serum metabolome during 22‐week US Army IMT. Fifty‐four volunteers (mean ± SD; 22 ± 3 year; 24.6 ± 3.7 kg/m2) completed this longitudinal study. Body composition measurements (InBody 770) and blood samples were collected under fasting, rested conditions PRE and POST IMT. Global metabolite profiling was performed to identify metabolites involved in energy, carbohydrate, lipid, and protein metabolism (Metabolon, Inc.). There was no change in body mass (POST‐PRE; 0.4 ± 5.1 kg, p = 0.59), while FM decreased (−1.7 ± 3.5 kg, p < 0.01), and FFM increased (2.1 ± 2.8 kg, p < 0.01) POST compared to PRE IMT. Of 677 identified metabolites, 340 differed at POST compared to PRE (p < 0.05, Q < 0.10). The majority of these metabolites were related to fatty acid (73%) and amino acid (26%) metabolism. Increases were detected in 41% of branched‐chain amino acid metabolites, 53% of histidine metabolites, and 35% of urea cycle metabolites. Decreases were detected in 93% of long‐chain fatty acid metabolites, while 58% of primary bile acid metabolites increased. Increases in amino acid metabolites suggest higher rates of protein turnover, while changes in fatty acid metabolites indicate increased fat oxidation, which likely contribute changes in body composition during IMT. Overall, changes in metabolomics profiles provide insight into metabolic adaptions underlying changes in body composition during IMT. [ABSTRACT FROM AUTHOR]

The dietary intake of branched-chain amino acids (BCAAs) has been reported to be associated with both elevated blood pressure (BP) and hypertension risk, while published findings were inconsistent, and the causality has never been well disclosed. We performed this prospective study aiming to find out the relationship between dietary BCAAs intake and hypertension risk in the Chinese population. A total of 8491 participants (40,285 person-years) were selected. The levels of dietary BCAAs intake were estimated using the 24-h Food Frequency Questionnaire. Associations of both BP values and hypertension risk with per standard deviation increase of BCAAs were estimated using linear and COX regression analysis, respectively. The hazard ratios and 95% confidence interval were given. Restricted cubic spline analysis (RCS) was used to estimate the nonlinearity. Both systolic and diastolic BP values at the end points of follow-up were positively associated with dietary BCAAs intake. Positive associations between BCAAs intake and hypertension risk were shown in both men and women. By performing a RCS analysis, the nonlinear relationship between BCAAs intake and hypertension was shown. As the intake levels of Ile, Leu, and Val, respectively, exceeded 2.49 g/day, 4.91 g/day, and 2.88 g/day in men (2.16 g/day, 3.84 g/day, and 2.56 g/day in women), the hypertension risk increased. Our findings could provide some concrete evidence in the primary prevention of hypertension based on dietary interventions. [ABSTRACT FROM AUTHOR]

Plasma levels of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) are considered early metabolic markers of obesity and insulin resistance (IR). This study aimed to assess changes in plasma concentrations of BCAA/AAA and HOMA-IR2 (homeostasis model assessment of IR) after intervention-induced modifications in fat mass (FM) and fat-free mass (FFM) among French Polynesian adolescents. FM, FFM, plasma levels of BCAA and AAA, HOMA-IR2 were recorded at baseline and post intervention among 226 adolescents during a 5-month school-based intervention on diet and physical activity. Participants were divided into two subgroups according to their college attendance status which determined their intervention adherence: externs/half-residents (n = 157) and residents (n = 69). Four ordinal categories of body composition changes post-intervention were created for the analysis (FMgain/FFMlost < FMgain/FFMgain < FMlost/FFMlost < FMlost/FFMgain). After 5 months, changes in BCAA (p−trend < 0.001) and AAA (p−trend = 0.007) concentrations were positively associated with ordinal categories of body composition. HOMA-IR2 significantly decreased with FMlost (−0.40; 95% CI, −0.60 to −0.20) and increased with FMgain (0.23; 95% CI, 0.11 to 0.36). Our results suggest that FM loss is associated with a decrease in concentrations of obesity and IR metabolic markers which is more substantial when FM loss is accompanied with FFM gain. [ABSTRACT FROM AUTHOR]

Context: While Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given body mass index (BMI), it remains unclear whether the same markers of metabolic pathways are associated with diabetes. Objective: We evaluated associations between metabolic biomarkers and incidence of T2D in 3 major Asian ethnic groups (Chinese, Malay, and Indian) and a European population. Methods: We analyzed data from adult males and females of 2 cohorts from Singapore (n = 6393) consisting of Chinese, Malays, and Indians and 3 cohorts of European-origin participants from Finland (n = 14 558). We used nuclear magnetic resonance to quantify 154 circulating metabolic biomarkers at baseline and performed logistic regression to assess associations with T2D risk adjusted for age, sex, BMI and glycemic markers. Results: Of the 154 metabolic biomarkers, 59 were associated with higher risk of T2D in both Asians and Europeans (P < 0.0003, Bonferroni-corrected). These included branched chain and aromatic amino acids, the inflammatory marker glycoprotein acetyls, total fatty acids, monounsaturated fatty acids, apolipoprotein B, larger very low-density lipoprotein particle sizes, and triglycerides. In addition, 13 metabolites were associated with a lower T2D risk in both populations, including omega-6 polyunsaturated fatty acids and larger high-density lipoprotein particle sizes. Associations were consistent within the Asian ethnic groups (all Phet ≥ 0.05) and largely consistent for the Asian and European populations (Phet ≥ 0.05 for 128 of 154 metabolic biomarkers). Conclusion: Metabolic biomarkers across several biological pathways were consistently associated with T2D risk in Asians and Europeans. [ABSTRACT FROM AUTHOR]

Context: Visceral (VAT) and subcutaneous adipose tissue (SAT) function as endocrine organs capable of influencing metabolic health across adiposity levels. Objective: We aimed to investigate whether metabolites associated with VAT and SAT impact metabolic health through metabolite concentrations. Methods: Analyses are based on 1790 participants from the population-based Rhineland Study. We assessed plasma levels of methionine (Met), branched-chain amino acids (BCAA), aromatic amino acids (AAA), and their metabolic downstream metabolites with liquid chromatography-mass spectrometry. VAT and SAT volumes were assessed by magnetic resonance imaging (MRI). Metabolically healthy and unhealthy phenotypes were defined using Wildman criteria. Results: Metabolically unhealthy participants had higher concentrations of BCAA than metabolically healthy participants (P < 0.001). In metabolically unhealthy participants, VAT volumes were significantly associated with levels of L-isoleucine, L-leucine, indole-3-lactic acid, and indole-3-propionic acid (in log SD units: β = 0.16, P = 0.003; β = 0.12, P = 0.038; β = 0.11, P = 0.035 and β = -0.16, P = 0.010, respectively). Higher concentrations of certain BCAA and AAA-downstream metabolites significantly increased the odds of cardiometabolic risk markers. The relation between VAT volume and cardiometabolic risk markers was mediated by BCAA (indirect effects 3.7%-11%, P = 0.02 to < 0.0001), while the effect of VAT on systemic inflammation was mediated through higher kynurenine concentrations (indirect effect 6.4%, P < 0.0001). Conclusion: Larger volumes of VAT in metabolically unhealthy individuals are associated with altered concentrations of circulating BCAA and AAA-downstream metabolites, increasing the odds of cardiometabolic risk markers. This suggests that these metabolites are involved in the mechanisms that underlie the relationship of abdominal VAT with metabolic health. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore associations of branched-chain amino acids (BCAA) in early pregnancy with gestational diabetes mellitus (GDM), and whether high BCAAs and lipidomics markers had interactive effects on the risk of GDM. Methods: We conducted a 1:1 case-control study (n = 486) nested in a prospective cohort of pregnant women in Tianjin, China. Blood samples were collected at their first antenatal care visit (median 10 gestational weeks). Serum BCAAs, saturated fatty acids (SFA) and lysophosphatidylcholines (LPC) were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional logistic regression was performed to examine associations of BCAAs with the risk of GDM. Interactions between high BCAAs and high SFA16:0 for GDM were examined using additive interaction measures. Results: High serum valine, leucine, isoleucine, and total BCAAs were associated with markedly increased risk of GDM (OR of top vs bottom tertiles: 1.91 [95% CI, 1.22-3.01]; 1.87 [1.20-2.91]; 2.23 [1.41-3.52]; 1.93 [1.23-3.02], respectively). The presence of high SFA16:0 defined as ≥ 17.1 nmol/mL (ie, median) markedly increased the ORs of high leucine alone and high isoleucine alone up to 4.56 (2.37-8.75) and 4.41 (2.30-8.43) for the risk of GDM, with significant additive interaction. After adjustment for LPCs, the ORs were greatly elevated (6.33, 2.25-17.80 and 6.53, 2.39-17.86) and the additive interactions became more significant. Conclusion: BCAAs in early pregnancy were positively associated with the risk of GDM, and high levels of leucine and isoleucine enhanced the risk association of high SFA16:0 with GDM, independent of LPCs. [ABSTRACT FROM AUTHOR]