BACKGROUND: Diets with high inclusion of corn co-products such as corn fermented protein (CFP) may contain excess Leu, which has a negative impact on feed intake and growth performance of pigs due to increased catabolism of Val and Ile and reduced availability of Trp in the brain for serotonin synthesis. However, we hypothesized that the negative effect of using CFP in diets for weanling pigs may be overcome if diets are fortified with crystalline sources of Val, Trp, and (or) Ile.
METHODS: Three hundred and twenty weanling pigs were randomly allotted to one of 10 dietary treatments in a completely randomized design, with 4 pigs per pen and 8 replicate pens per treatment. A corn-soybean meal diet and 2 basal diets based on corn and 10% CFP or corn and 20% CFP were formulated. Seven additional diets were formulated by fortifying the basal diet with 20% CFP with Ile, Trp, Val, Ile and Val, Ile and Trp, Trp and Val, or Ile, Trp and Val. A two-phase feeding program was used, with d 1 to 14 being phase 1 and d 15 to 28 being phase 2. Fecal scores were recorded every other day. Blood samples were collected on d 14 and 28 from one pig per pen. On d 14, fecal samples were collected from one pig per pen in 3 of the 10 treatments to determine volatile fatty acids, ammonium concentration, and microbial protein. These pigs were also euthanized and ileal tissue was collected.
RESULTS: There were no effects of dietary treatments on any of the parameters evaluated in phase 1. Inclusion of 10% or 20% CFP in diets reduced (P < 0.05) final body weight on d 28, and average daily gain (ADG) and average daily feed intake (ADFI) in phase 2 and for the entire experimental period. However, pigs fed the CFP diet supplemented with Val, Ile, and Trp had final body weight, ADFI, ADG and gain to feed ratio in phase 2 and for the entire experiment that was not different from pigs fed the control diet. Fecal scores in phase 2 were reduced (P < 0.05) if CFP was used.
CONCLUSIONS: Corn fermented protein may be included by up to 20% in diets for weanling pigs without affecting growth performance, gut health, or hindgut fermentation, if diets are fortified with extra Val, Trp, and Ile. Inclusion of CFP also improved fecal consistency of pigs.

Branched-chain amino acids (BCAAs)-leucine (Leu), isoleucine (Ile), and valine (Val)-are essential nutrients with significant roles in protein synthesis, metabolic regulation, and energy production. This review paper offers a detailed examination of the physico-chemical properties of BCAAs, their industrial synthesis, and their critical functions in various biological processes. The unique isomerism of BCAAs is presented, focusing on analytical challenges in their separation and quantification as well as their solubility characteristics, which are crucial for formulation and purification applications. The industrial synthesis of BCAAs, particularly using bacterial strains like Corynebacterium glutamicum, is explored, alongside methods such as genetic engineering aimed at enhancing production, detailing the enzymatic processes and specific precursors. The dietary uptake, distribution, and catabolism of BCAAs are reviewed as fundamental components of their physiological functions. Ultimately, their multifaceted impact on signaling pathways, immune function, and disease progression is discussed, providing insights into their profound influence on muscle protein synthesis and metabolic health. This comprehensive analysis serves as a resource for understanding both the basic and complex roles of BCAAs in biological systems and their industrial application.

Cellular senescence, a process in which a cell exits the cell cycle in response to stressors, is one of the hallmarks of aging. Senescence and the senescence-associated secretory phenotype (SASP)-a heterogeneous set of secreted factors that disrupt tissue homeostasis and promote the accumulation of senescent cells-reprogram metabolism and can lead to metabolic dysfunction. Dietary interventions have long been studied as methods to combat age-associated metabolic dysfunction, promote health, and increase lifespan. A growing body of literature suggests that senescence is responsive to diet, both to calories and specific dietary macronutrients, and that the metabolic benefits of dietary interventions may arise in part through reducing senescence. Here, we review what is currently known about dietary macronutrients\' effect on senescence and the SASP, the nutrient-responsive molecular mechanisms that may mediate these effects, and the potential for these findings to inform the development of a nutrigeroscience approach to healthy aging.

UNASSIGNED: Mental health disorders are one of the most important and increasing health problems in the youth of today\'s societies. Some dietary intake and body mass status are factors that affect mental health. This study aimed to investigate the relationship between the intake of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) and anthropometric and dietary inflammatory indices with mental health, including depression, anxiety, and stress.
UNASSIGNED: In this case-control study, the data of 138 teenage girls aged 13-18 years were collected. Three-day 24-hour food recall and standard anthropometric methods were used to calculate the dietary inflammation intake score of normal and energy-adjusted diets. Mental health disorders were diagnosed by the DASS-21 questionnaire. Statistical analysis used Student\'s t-test, correlation, and multiple regression were used to analyze the data based on the study\'s statistical requirements.
UNASSIGNED: Based on the findings, 59 (42%) of the girls had mental disorders, and 79 (58%) were healthy. The average weight of stressed people was significantly higher than that of healthy people, and the BMI of anxious people was significantly higher than that of nonanxious people (P < 0.05). A significant positive correlation was found between stress and weight and energy intake. Additionally, there was a significant negative correlation between BCAAs and mental health. The average intake of BCAAs was significantly lower in patients (P = 0.01). The trend analysis showed significantly lower BCAA levels among the 4th quartile of mental disorders. No significant relationship was observed between DII, AAA, and anthropometric indices. After adjustment of the results, no relationship was observed between mental health and the studied factors.
UNASSIGNED: BCAA might be related to mental health. Further studies in different age and sex groups are highly recommended.

Aim: Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were suggested as potential biomarkers in liver disease. This study aimed to develop and validate a simple and rapid LC-MS/MS method to simultaneously measure serum BCAAs and AAAs levels in patients with liver injury, and further establish reference intervals of Chinese healthy adult populations.Patients & methods: Samples were prepared by a one-step protein precipitation and analysis time was 4 min per run.Results: The validation results showed good linearity (r2 >0.9969), satisfactory accuracy (94.44% - 107.75%) and precision (0.10% - 5.90%).Conclusion: This method proved to be suitable for high-throughput routine clinical use and could be a valuable adjunct diagnosis tool for liver injury and other clinical applications.
[Box: see text].

OBJECTIVE: This study aimed to investigate branched-chain amino acid (BCAA) catabolism in diabetic retinopathy (DR).
METHODS: Wild-type and db/db mice were fed BCAAs (5 or 10 mg/kg/day) for 12 weeks, and hyperglycemia-exposed Müller cells were treated with BCAAs (2 or 5 mmol/L) for 24 and 48 h. BCAA levels were measured using MS/MS. Western blotting was performed to detect proteins. Flow cytometry, oxygen consumption rate, and Cell Counting Kit-8 assays were used to evaluate Müller cell viability. Each experiment was conducted at least thrice.
RESULTS: BCAAs and branched-chain α-keto acids (BCKAs) were increased in the retina and systemic tissues of diabetic mice, and these changes were further enhanced to approximately 2-fold by extra BCAAs compared to wild-type group. In vitro, BCAAs and BCKAs were induced in hyperglycemic Müller cells, and augmented by BCAA supplementation. The aberrant BCAA catabolism was accompanied by mTORC1 activation and subsequently induced TNF-ɑ, VEGFA, GS, and GFAP in retinas and Müller cells under diabetic conditions. The cell apoptosis rate increased by approximately 50%, and mitochondrial respiration was inhibited by hyperglycemia and BCAA in Müller cells. Additionally, mTORC1 signaling was activated by leucine in Müller cells. Knockdown of Sestrin2 or LeuRS significantly abolished the leucine-induced mTORC1 phosphorylation and protected Müller cell viability under diabetic conditions.
CONCLUSIONS: We found that BCAA catabolism is hindered in DR through mTORC1 activation. Leucine plays a key role in inducing mTORC1 by sensing Sestrin2 in Müller cells. Targeting Sestrin2 may ameliorate the toxic effects of BCAA accumulation on Müller cells in DR.

Background: The relationship between gut microbiota and diabetes-related amino acids significantly impacts insulin resistance and obesity. We aimed to quantify two Bacteroidetes species and their correlation with branched-chain amino acids, aromatic amino acids, and glutamate in prediabetes (preDM) and type 2 diabetes mellitus (T2DM). Methods: Fecal samples were collected from 68 participants, including 21 with T2DM, 23 with preDM, and 24 with normal glycemic tolerance (NGT). The abundance of Bacteroides vulgatus and Bacteroides thetaiotaomicron was determined by quantitative real-time polymerase chain reaction. Plasma amino acid measurements were performed using liquid chromatography coupled with tandem mass spectrometry. Results: The quantities of B. vulgatus and B. thetaiotaomicron were reduced in preDM and T2DM than in NGT subjects, but it was not statistically significant. The concentrations of leucine, valine, and tyrosine were significantly higher in preDM and T2DM than in NGT subjects (P < 0.05). A negative correlation was observed between B. thetaiotaomicron abundance and two aromatic amino acids (tyrosine, r = -0.28, P = 0.04; phenylalanine, r = -0.26, P = 0.05). Conclusions: These findings imply that, since gut microbiota varies throughout ethnic groups, further research with many participants will be required to determine the abundance of B. vulgatus and B. thetaiotaomicron in preDM and T2DM and their association with diabetes-related amino acids.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

BACKGROUND: The association of hypertension (HTN) and different types of dietary amino acids is not yet clear. The aim of the present study was to investigate the association of branch chain amino acids (BCAAs) and the prevention of HTN.
METHODS: This cross-sectional study was conducted on 4184 people aged 35 to 70 using data from the Sabzevar Persian cohort study in Sabzevar, Iran. Data on dietary intake of BCAAs including leucine, isoleucine, and valine were obtained using a validated Food Frequency Questionnaire (FFQ). Multivariable logistic regression analysis assessed the link between HTN and BCAAs.
RESULTS: The results showed that participants with HTN had a higher total protein and BCAAs intake than participants with normal BP (P < 0.01). A marginally significant association was found between the risk of HTN with the total intake of BCAAs (OR = 1.018, CI95%: 1.001-1.035, P = 0.04), leucine (OR = 1.040, CI95%:1.002-1.080, P = 0.03), isoleucine (OR = 1.068, CI95%:1.001-1.140, P = 0.04), and valine (OR = 1.060, CI95%:1.003-1.121, P = 0.04). However, the association disappeared after adjusting the total protein and calorie intake.
CONCLUSIONS: The results indicated that the dietary intake of BCAAs may be associated with the risk of HTN. Future longitudinal research is warranted.