Dietary Essential Amino Acids Research Articles

Endurance training and essential amino acid intervention synergize to ameliorate fructose-induced metabolic dysfunction in mice

Purpose: Excessive fructose (FRU) consumption can rapidly produce multiple features of metabolic syndrome, including dysregulation of systemic metabolism, insulin resistance, and diabetes. Essential amino acids (EAAs) and endurance exercise training (ET) improve abnormal metabolism in various disease conditions, yet their combined effect and metabolic mechanism remain unclear. Thus, the current study aimed to investigate metabolic kinetic mechanism and the combined effect of EAA and ET on fructose-induced metabolic dysfunction. Materials and methods: Mice were randomly divided into 5 groups with an 8-week intervention: normal chow (CON), FRU, FRU+ET, FRU+EAA or FRU+ET+ EAA, followed by stable isotope tracer infusions ([U-13C16]palmitate, [D2]glucose, and [D5]glycerol) or D2O administration to determine substrate metabolic flux rates and their contribution to TCA cycle flux and protein synthesis rates of various organs, respectively. Summary of results: FRU-induced adverse changes in body weight and physical function were reversed by ET, EAA, or ET+EAA. In stable isotope tracing analysis, ET and ET+EAA alleviated hyperglycemia by suppressing hepatic glucose production rate, while EAA and ET+EAA normalized palmitate turnover and contribution to TCA cycle in various organs. Additionally, the altered protein synthesis measured using a D2O labeling method was normalized by ET and ET+EAA. Conclusion:These findings suggest that the combined treatment of dietary EAAs and ET more effectively mitigates fructose-induced metabolic dysfunction by normalizing hepatic glucose production rate, protein synthesis rates, and fatty acid metabolism. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI22C2208), and the National Research Foundation of Korea (NRF), funded by the Korea government (MSIT) (No. 2021R1A2C3005801), and partially funded by MYOCARE INC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Assessment of four different dietary amino acid profiles recommended for ISA Brown layer hens: A validation study

The current feeding study was designed to validate the two dietary essential amino acid profiles (EAAP) established based on linear broken-line (LBL) and quadratic broken-line (QBL) models, in a previous study, against Evonik (AMINOHen) and breeder recommendations for ISA Brown layers for peak production (PP, 20 to 44 weeks of age), and post peak production (post PP, 44 to 75 weeks of age). The EAAP based on LBL models on average had 19.5% and 26.0% lower digestible AA (Lys, Met + Cys, Thr, Trp, Ile and Val), than the EAAP based on QBL models for PP and post PP, respectively. The EAAP based on AMINOHen and breeder recommendation had lower digestible AA than QBL, and higher EAAP than LBL models for both production phases. At 20 weeks of age, 224 ISA Brown layer hens were weighed and randomly allocated to individual battery cages. Each of the four diets was replicated 8 times with 7 birds per replicate. Egg production was recorded daily, and egg weights were measured at the end of each week. Feed consumption was measured at the end of each period. The egg production rate was not significantly affected by the diets and remained at around 98.0% (PP) and 95.0% (post PP) (P > 0.05). Birds fed diets based on LBL recommendation consistently laid smaller eggs, resulting in a lower egg mass (59.8 vs. 62.0 g egg/hen per day during PP, and 60.3 vs. 63.0 g egg/hen per day during post PP; P < 0.05). Diets had no significant effect on feed intake and body weight (P > 0.05). The highest feed conversion ratio (FCR) during PP (P = 0.067) and post PP (P < 0.05) was recorded for the birds offered diets based on LBL recommendation. In conclusion, all four EAAP tested in this study support an above average egg production rate. However, the EAAP based on LBL models may potentially decrease the input feed cost per kilogram of eggs but are not set to optimise FCR and maximise egg mass.

Evaluation of Dietary Essential Amino Acid Supplementation on Growth, Digestive Capacity, Antioxidant, and Intestine Health of the Juvenile Redclaw Crayfish, Cherax quadricarinatus.

The present study was an 8-week feeding trial investigating the effects of lysine and threonine supplementation in vegetable-based diets on growth, antioxidative capacity, and gut microbiota of juvenile redclaw crayfish, Cherax quadricarinatus (initial weight 11.52 ± 0.23 g). The lysine and threonine were supplemented to formulate five isonitrogenous (37%) and isolipidic (9%) diets containing 0% (control), 0.2% lysine (L0.2), 0.2% threonine (T0.2), 0.4% lysine (L0.4), and 0.4% threonine (T0.4), respectively. Compared to the control, weight gain rate (WGR) and specific growth rate (SGR) of C. quadricarinatus significantly increased with increasing dietary lysine and threonine supplementation from 0.2% to 0.4% (P < 0.05). Hepatopancreas trypsin activity significantly increased with increasing levels of lysine and threonine in diets (P < 0.05). However, the pepsin, lipase, and amylase activities were not affected by dietary levels of lysine and threonine (P > 0.05). Compared with the control, crayfish in T0.4 and L0.4 showed significantly higher glutathione peroxidase (GPx) activity (P < 0.05), lower alanine aminotransferase (ALT) activity, and lower malondialdehyde (MDA) content (P < 0.05). Supplementation with 0.4% lysine significantly changed the composition of the gut microbiota (P < 0.05), which showed a significantly increased relative abundance of Proteobacteria and decreased Firmicutes, Actinomycetes, and Pontomyces (P < 0.05). The PICRUSt analysis demonstrated that the abundance of the metabolism and cellular processes pathways in the L0.4 group were markedly decreased compared with the control (P < 0.05). Meanwhile, a tighter interaction of the microbiota community in crayfish was observed in the T0.4 experimental group. In conclusion, these results suggested that dietary supplementation with 0.4% threonine could significantly promote growth and improve microbial health in juvenile C. quadricarinatus.

Essential amino acid requirements of fish and crustaceans, a meta‐analysis

AbstractA meta‐analysis of literature data on essential amino acid (EAA) requirements of fish and crustaceans was performed to re‐estimate EAA requirements and provide ideal amino acid profiles. Large numbers of studies have been conducted on EAA requirements of fish and crustaceans over the past decades. However, estimated EAA requirements of different species showed a large variation due to differences in methodological approaches and regression models. An extensive search and inclusion of literature on EAA requirements were conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines in this study, resulting in a dataset of 358 studies covering 77 species. The relative percentage of maximum weight gain was used as the outcome to evaluate the 10 EAA requirements. Forest plots analysis was employed for heterogeneity analysis, study weight allocation and re‐estimation of the requirements. Results showed that trophic level, water temperature and dietary EAA inclusion levels affected EAA requirements estimation. The meta‐analysis suggested that the estimated 10 EAA requirements (expressed as % crude protein, CP) of the fish were: arginine (Arg) 5.0 (±0.14), histidine (His) 2.0 (±0.11), isoleucine (Ile) 3.3 (±0.16), leucine (Leu) 4.9 (±0.24), valine (Val) 3.8 (±0.11), lysine (Lys) 5.2 (±0.12), sulfur amino acids (Met + Cys) 3.5 (±0.18), total aromatic amino acids (Phe + Tyr) 6.2 (±0.12), threonine (Thr) 3.5 (±0.18) and tryptophan (Trp) 0.9 (±0.08). Estimated EAA requirements (expressed as % CP) of crustaceans were Arg 5.1 (±0.31), His 2.5 (±0.15), Ile 4.3 (±0.97), Leu 5.7 (±0.08), Val 4.3 (±0.30), Lys 4.9 (±0.28), Met + Cys 3.2 (±0.18), Phe + Tyr 5.1 (±0.65), Thr 3.8 (±0.04) and Trp 0.8 (±0.15).

Growth Performance and Nutrient Utilization of Clarias. gariepinus Fed Soaked Boscia senegalensis Supplemented Diets

The present study investigated the nutritional suitability and cost effectiveness of a Sahelian plant seeds, Aizien (Boscia senegalensis) as alternative to Soy bean meal in the diet of African Catfish (Clarias gariepinus Burchell, 1822). Raw seeds of the B. senegalensis were subjected to processing method intended to reduce levels of the most important antinutritional factors (ANFs). The resultant product was used to formulate five isonitrogenous (40%) diets, containing the seed meals at inclusion levels of 25% to 100% of dietary protein and fed to Fingerlings of the African Catfish at 5% of their body weight for a period of 24 weeks. The feeding trial involved one hundred and fifty (150) fingerlings of C. gariepinus(2.43g –3.10g) randomly stocked at ten fish per Tank (200L) in a non-flow through design with regular water replacement and water quality monitoring. Important growth performance and nutrient utilization indices, weight gain (WG), specific growth rate (SGR), feed conversion ratio (FCR), protein efficiency ratio (PER), and Feed conversion efficiency (FCE) of fish in the experimental groups fed SBS based showed that Fish fed 50% SBS diet recorded the highest WG (439.14g), SGR (1.34%/day) and FCR (1.35). This could be attributed to the protein quality of the diets in relation to the dietary essential amino acid profile of the experimental diets used. Generally, the Fish fed the 100%SBS diet recorded the lowest growthperformance with regards to WG (360.68g), SGR(1.25), FCR (1.61), PER (1.58) and FCE (62.22%).From the results of this experiment, for better production of African catfish C. gariepinus, replacement levels of 50 SBS may serve as good alternative to SBM in feed formulation for C. gariepinus.

Growth performance, caecal microbiome profile, short-chain fatty acids, and litter characteristics in response to placement on reused litter and combined threonine, arginine and glutamine supplementation to juvenile male broiler chickens

BackgroundExposure of broilers to litter microbiome may increase specific amino acid (AA) requirements towards activated immune responses. This may challenge the generality of the ideal protein (IP) concept, in which dietary essential AA to lysine ratios aimed to mimic presumably constant AA to lysine ratios in whole bird requirements. Therefore, we tested the effect of threonine, arginine and glutamine (TAG) supplementation to IP-based control diets (C) on performance, caecal microbiome composition, short-chain fatty acids and litter characteristics of broiler chickens placed on reused litter.ResultsThirty-two pens with ten male broiler chickens each were used in a 2 × 2 factorial arrangement of two diet treatments (with or without TAG supplementation) and two litter treatments (placement on clean or reused litter) for 21 days (n = 8). Caecal contents were analysed for microbiome profile using percent guanine + cytosine (%G + C profile) method and short chain fatty acids. TAG-supplemented birds underperformed compared to C birds (P = 0.002), whereas birds placed on reused litter outperformed those on clean litter (P = 0.047). Diet, reused litter and their interaction impacted the %G + C profile at different ranges. Whilst TAG supplementation reduced bacterial abundance at %G + C 51–56 (P < 0.05), reused litter placement tended to reduce %G + C 23–31 and increase %G + C 56–59 (P < 0.10). However, TAG supplementation reduced bacterial abundance at %G + C 47–51 (P < 0.05) and increased caecal branched chain fatty acids on clean litter only (P = 0.025). Greater levels of propionic acid were observed for C birds placed on reused litter only (P = 0.008). Litter pH was greater for reused litter pens than clean litter pens at day 21 (P < 0.001). In addition, litter moisture content was less for TAG birds and reused litter pens compared to C birds (P = 0.041) and clean litter pens (P < 0.001), respectively.ConclusionsThese data support the view that irrespective of performance benefits arising from bird placement on reused litter, TAG supplementation to IP-formulated baseline rations impaired growth, supported by the lowered abundance of caecal bacteria known to dominate in well-performing birds and greater levels of caecal branched chain fatty acids.

Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrome. We aim to study the molecular mechanisms and effects on cardiac function in rodents with HFrEF of a designer diet in which free essential amino acids-in specifically designed percentages-substituted for protein. Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricle (LV) pressure overload or sham surgery. Whole-body glucose homeostasis was studied with glucose tolerance test, while myocardial dysfunction and fibrosis were measured with echocardiogram and histological analysis. Mitochondrial bioenergetics and morphology were investigated with oxygen consumption rate measurement and electron microscopy evaluation. Circulating and cardiac non-targeted metabolite profiles were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy, while RNA-sequencing was used to identify signalling pathways mainly affected. The amino acid-substituted diet shows remarkable preventive and therapeutic effects. This dietary approach corrects the whole-body glucose metabolism and restores the unbalanced metabolic substrate usage-by improving mitochondrial fuel oxidation-in the failing heart. In particular, biochemical, molecular, and genetic approaches suggest that renormalization of branched-chain amino acid oxidation in cardiac tissue, which is suppressed in HFrEF, plays a relevant role. Beyond the changes of systemic metabolism, cell-autonomous processes may explain at least in part the diet's cardioprotective impact. Collectively, these results suggest that manipulation of dietary amino acids, and especially essential amino acids, is a potential adjuvant therapeutic strategy to treat systolic dysfunction and HFrEF in humans.

Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R.gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R.gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R.gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.

Higher Intake of Total Dietary Essential Amino Acids Is Associated with a Lower Prevalence of Metabolic Syndrome among Korean Adults.

We hypothesized that a well-balanced intake of total essential amino acids (EAAs) may be associated with lower prevalence of metabolic syndrome among Korean adults. This population-based cross-sectional study included 25,787 participants aged ≥30 years from the 2008-2019 Korea National Health and Nutrition Examination Survey. Dietary information was obtained from 24 h recall data. Demographic and lifestyle factors were assessed using self-administered questionnaires, and metabolic biomarkers were obtained from a health examination. Total essential amino acid score (EAAS) was calculated to determine whether essential amino acid (EAA) intake meets the recommended nutrient intake (RNI). Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. After adjusting for multiple confounding factors, participants with higher EAAS had a significantly lower prevalence of high blood pressure (OR: 0.86, 95% CI: 0.75-0.98), hypertriglyceridemia (OR: 0.86, 95% CI: 0.76-0.98), and Metabolic syndrome (MetS) (OR: 0.86, 95% CI: 0.74-0.996). Spline regression analysis confirmed linearity of the association between total EAAS and MetS. EAA intake and MetS are associated with an inverse dose-response relationship in which metabolic disease may be prevented when the overall EAA intake meets the RNI.

Resistance Exercise Training When Combined With Dietary Essential Amino Acids Enhances Strength, Endurance, And Insulin Sensitivity

Resistance Exercise Training When Combined With Dietary Essential Amino Acids Enhances Strength, Endurance, And Insulin Sensitivity

Purple bacteria screening for photoautohydrogenotrophic food production: Are new H2-fed isolates faster and nutritionally better than photoheterotrophically obtained reference species?

Photoautohydrogenotrophic enrichments of wastewater treatment microbiomes were performed to obtain hypothetically high-potential specialist species for biotechnological applications. From these enrichment cultures, ten photoautohydrogenotrophic species were isolated: six Rhodopseudomonas species, three Rubrivivax members and Rhodobacter blasticus. The performance of these isolates was compared to three commonly studied, and originally photoheterotrophically enriched species (Rhodopseudomonas palustris, Rhodobacter capsulatus and Rhodobacter sphaeroides), designated as reference species. Repeated subcultivations were applied to improve the initial poor performance of the isolates (acclimation effect), which resulted in increases in both maximum growth rate and protein productivity. However, the maximum growth rate of the reference species remained 3–7 times higher compared to the isolates (0.42–0.84 d−1 at 28 °C), while protein productivities remained 1.5–1.7 times higher. This indicated that H2-based enrichment did not result in photoautohydrogenotrophic specialists, suggesting that the reference species are more suitable for intensified biomass and protein production. On the other hand, the isolates were able to provide equally high protein quality profiles as the references species, providing full dietary essential amino acid matches for human food. Lastly, the effect of metabolic carbon/electron switching (back and forth between auto- to heterotrophic conditions) initially boosted µmax when returning to photoautohydrogenotrophic conditions. However, the switch negatively impacted lag phase, protein productivities and pigment contents. In the case of protein productivity, the acquired acclimation was partially lost with decreases of up to 44 % and 40 % respectively for isolates and reference species. Finally, the three reference species, and specifically Rh. capsulatus, remained the most suitable candidate(s) for further biotechnological development.

O89 Ideal relationship among dietary essential amino acids for Pacu in the finishing growth phase

O89 Ideal relationship among dietary essential amino acids for Pacu in the finishing growth phase

Dietary Essential Amino Acid Intake Is Associated with High Muscle Strength in Korean Older Adults.

The relationship between daily dietary intake of an individual or all essential amino acids (EAAs) and muscle strength in older adults is still inadequately characterized. This population-based cross-sectional study included 5971 participants aged ≥65 years from the 2014–2019 Korea National Health and Nutrition Examination Survey. Dietary information was derived from the 24 h recall data. Total essential amino acid score (EAAS) was calculated with an intake that satisfied the recommended nutrient intake (RNI) in each essential amino acid (EAA). The mean handgrip strength was estimated from triplicate measurements obtained using the dominant hand, and high muscle strength was defined as handgrip strength ≥28 kg for men and ≥18 kg for women. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. After multivariable adjustment, we found that a high total EAAS was associated with high muscle strength in Korean older adults (OR: 1.38, 95% CI: 1.07–1.79). High muscle strength was significantly enhanced with increased total EAA intake from animal sources (OR: 1.27, 95% CI: 1.02–1.58), but there was no significant association with total EAA intake from non-animal sources. EAA intake and high muscle strength are associated based on a positive dose-response relationship in which high muscle strength is further increased when the overall EAA intake meets the RNI. Thus, Korean older adults should ensure an adequate intake of all EAAs from various food sources (especially animal sources) to meet the RNI as a prerequisite for achieving high muscle strength.

Prevention of Loss of Muscle Mass and Function in Older Adults during COVID-19 Lockdown: Potential Role of Dietary Essential Amino Acids.

As the COVID-19 pandemic became a global emergency, social distancing, quarantine, and limitations in outdoor activities have resulted in an environment of enforced physical inactivity (EPI). A prolonged period of EPI in older individuals accelerates the deterioration of skeletal muscle health, including loss of muscle mass and function, commonly referred to as sarcopenia. Sarcopenia is associated with an increased likelihood of the progression of diabetes, obesity, and/or depression. Well-known approaches to mitigate the symptoms of sarcopenia include participation in resistance exercise training and/or intake of balanced essential amino acids (EAAs) and high-quality (i.e., containing high EEAs) protein. As the pandemic situation discourages physical exercise, nutritional approaches, especially dietary EAA intake, could be a good alternative for counteracting against EPI-promoted loss of muscle mass and function. Therefore, in the present review, we cover (1) the impact of EPI-induced muscle loss and function on health, (2) the therapeutic potential of dietary EAAs for muscle health (e.g., muscle mass and function) in the EPI condition in comparison with protein sources, and finally (3) practical guidelines of dietary EAA intake for optimal anabolic response in EPI.

Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific.

Dietary removal of an essential amino acid (EAA) triggers the integrated stress response (ISR) in liver. Herein, we explored the mechanisms that activate the ISR and execute changes in transcription and translation according to the missing EAA. Wild‐type mice and mice lacking general control nonderepressible 2 (Gcn2) were fed an amino acid complete diet or a diet devoid of either leucine or sulfur amino acids (methionine and cysteine). Serum and liver leucine concentrations were significantly reduced within the first 6 h of feeding a diet lacking leucine, corresponding with modest, GCN2‐dependent increases in Atf4 mRNA translation and induction of selected ISR target genes (Fgf21, Slc7a5, Slc7a11). In contrast, dietary removal of the sulfur amino acids lowered serum methionine, but not intracellular methionine, and yet hepatic mRNA abundance of Atf4, Fgf21, Slc7a5, Slc7a11 substantially increased regardless of GCN2 status. Liver tRNA charging levels did not correlate with intracellular EAA concentrations or GCN2 status and remained similar to mice fed a complete diet. Furthermore, loss of Gcn2 increased the occurrence of ribosome collisions in liver and derepressed mechanistic target of rapamycin complex 1 signal transduction, but these changes did not influence execution of the ISR. We conclude that ISR activation is directed by intracellular EAA concentrations, but ISR execution is not. Furthermore, a diet devoid of sulfur amino acids does not require GCN2 for the ISR to execute changes to the transcriptome.

Injectable Dual-Dynamic-Bond Cross-Linked Hydrogel for Highly Efficient Infected Diabetic Wound Healing.

Diabetic wound is a significant challenge for clinical treatment with high morbidity and mortality. Plenty of hydrogels with good biocompatibility have been widely used in diabetic wound healing. However, most of them cannot be directly absorbed and utilized by the wounds, which prolongs the regeneration time. Here a new type of healing hydrogel is developed that is based on histidine, a natural dietary essential amino acid that is significant for tissue formation. The amino acid is cross-linked with zinc ions (Zn2+ ) and sodium alginate (SA) via dynamic coordinate and hydrogen bonds, respectively, forming a histidine-SA-Zn2+ (HSZH) hydrogel with good injectable, adhesive, biocompatible, and antibacterial properties. Application of this dual-dynamic-bond cross-linked HSZH hydrogel accelerates the migration and angiogenesis of skin-related cells in vitro. Furthermore, it significantly promotes the healing of infected diabetic wounds in vivo and uniquely allows a full repair of wounds within ≈13 days, while ≈27 days are required for the healing process of the control group. This work provides a new strategy for designing wound dressing materials, that weakly cross-linked material based on tissue-friendly micromolecules can heal the wounds more efficiently than highly cross-linked materials based on long-chain polymers.

119 A Meta-Regression Analysis to Evaluate the Influence of Branched-Chain Amino Acids in Lactation Diets on Sow and Litter Growth Performance

Abstract The branched-chain amino acids (BCAA) Ile, Leu, and Val are 3 dietary essential amino acids for lactating sows; however, effects of dietary BCAA on sow and litter growth performance in the literature are equivocal. Thus, a meta-regression analysis was conducted to evaluate effects of BCAA and their interactions in lactating sow diets to predict litter growth performance, sow bodyweight (BW) change, and sow feed intake. Thirty-four publications representing 43 trials from 1997 to 2020 were used to develop a database that contained 167 observations. Diets for each trial were reformulated using NRC (2012) nutrient loading values in an Excel-based spreadsheet. Amino acids were expressed on a standardized ileal digestible (SID) basis. Regression model equations were developed with the MIXED procedure of SAS (Version 9.4, SAS Institute, Cary, NC), and studies were weighted by the inverse of the squared SEM. Statistically significant (P &amp;lt; 0.05) predictor variables were assessed with a step-wise manual forward selection and required to provide an improvement of at least 2 BIC for model inclusion. Significant predictor variables within 3 equations developed for litter ADG included the count of weaned pigs per litter, dietary concentrations of NE, SID Lys, and CP, sow ADFI, Val:Lys, Ile:Lys, and Leu:Val. For sow BW change, significant predictor variables within 2 developed models included litter size at 24 h, sow ADFI, Leu:Lys, and Ile+Val:Leu. The optimum equation for sow ADFI included Leu:Trp, SID Lys, NE, CP, and Leu:Lys as significant predictor variables. Overall, the prediction equations suggest that BCAA have an important role in litter growth, sow BW change, and feed intake during lactation; however, the influence of BCAA on these criteria is much smaller than that of other dietary components such as NE, SID Lys, sow ADFI, and CP.

Metabolomic Workflow for the Accurate and High-Throughput Exploration of the Pathways of Tryptophan, Tyrosine, Phenylalanine, and Branched-Chain Amino Acids in Human Biofluids.

The modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.

A meta-regression analysis to evaluate the influence of branched-chain amino acids in lactation diets on sow and litter growth performance.

The branched-chain amino acids (BCAA) Ile, Leu, and Val are three dietary essential amino acids for lactating sows; however, effects of dietary BCAA on sow and litter growth performance in the literature are equivocal. Thus, a meta-regression analysis was conducted to evaluate the effects of BCAA and their interactions in lactating sow diets to predict litter growth performance, sow bodyweight change, and sow feed intake. Thirty-four publications that represented 43 trials from 1997 to 2020 were used to develop a database that contained 167 observations. Diets for each trial were reformulated using NRC. 2012. Nutrient requirements of swine. 11th ed. Washington, DC: National Academies Press nutrient loading values in an Excel-based spreadsheet. Amino acids were expressed on a standardized ileal digestible (SID) basis. Regression model equations were developed with the MIXED procedure of SAS (Version 9.4, SAS Institute, Cary, NC) and utilized the inverse of reported squared SEM with the WEIGHT statement to account for heterogeneous errors across studies. Predictor variables were assessed with a step-wise manual forward selection for model inclusion. Additionally, statistically significant (P < 0.05) predictor variables were required to provide an improvement of at least 2 Bayesian information criterion units to be included in the final model. Significant predictor variables within three optimum equations developed for litter ADG included the count of weaned pigs per litter, NE, SID Lys, CP, sow ADFI, Val:Lys, Ile:Lys, and Leu:Val. For sow BW change, significant predictor variables within two developed models included litter size at 24 h, sow ADFI, Leu:Lys, and Ile + Val:Leu. The optimum equation for sow ADFI included Leu:Trp, SID Lys, NE, CP, and Leu:Lys as significant predictor variables. Overall, the prediction equations suggest that BCAA play an important role in litter growth, sow BW change, and feed intake during lactation; however, the influence of BCAA on these criteria is much smaller than that of other dietary components such as NE, SID Lys, sow ADFI, and CP.

Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with no approved drugs. High-protein dietary intervention is currently the most effective treatment. However, its underlying mechanism is unknown. Here, using Drosophila oenocytes, the specialized hepatocyte-like cells, we find that dietary essential amino acids ameliorate hepatic steatosis by inducing polyubiquitination of Plin2, a lipid droplet-stabilizing protein. Leucine and isoleucine, two branched-chain essential amino acids, strongly bind to and activate the E3 ubiquitin ligase Ubr1, targeting Plin2 for degradation. We further show that the amino acid-induced Ubr1 activity is necessary to prevent steatosis in mouse livers and cultured human hepatocytes, providing molecular insight into the anti-NAFLD effects of dietary protein/amino acids. Importantly, split-intein-mediated trans-splicing expression of constitutively active UBR2, an Ubr1 family member, significantly ameliorates obesity-induced and high fat diet-induced hepatic steatosis in mice. Together, our results highlight activation of Ubr1 family proteins as a promising strategy in NAFLD treatment.