Dietary Amino Acids Research Articles

Open-labelled study to monitor the effect of an amino acid formula on symptom management in children with spinal muscular atrophy type I: The SMAAF pilot study.

An increasing number of families with children who have spinal muscular atrophy (SMA) are incorporating a special amino acid diet into their child's feeding regimens. Characteristics of the diet include high-carbohydrate and low-fat content with added probiotics. However, because of insufficient evidenced-based research, clinicians are unable to prescribe or endorse this diet. Our aim was to assess the tolerability of an adapted version of the traditional amino acid diet in children with SMA type I. Children with SMA type I were recruited if they were enterally fed and experienced at least one gastrointestinal symptom (reflux, vomiting, constipation, and/or diarrhea). Children were transitioned to an amino acid formula (Neocate Syneo-Nutricia) for 8 weeks. Feeding tolerance was measured weekly by telephone consultation to monitor reflux, vomiting, stool consistency, and frequency. Fourteen children were recruited, the mean age was 4.1 years (±1.2 SD), and 64% of participants were female. The mean resting energy expenditure determined by indirect calorimetry was 51.5 kcal/kg (±7 SD). The most common gastrointestinal complaint before switching to the amino acid formula was constipation, which was reported in 12 of 14 (85%) patients, of which 10 of the 12 (83%) children required daily stool softeners/laxatives to help regulate bowel function. After 8 weeks on the amino acid formula, 10 out of 12 (83%) children stopped or reduced constipation medication. Children with SMA type I who display gastrointestinal symptoms such as constipation and reflux may benefit from an amino acid formula that is fortified with probiotics.

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.

An Elemental Diet Enriched in Amino Acids Alters the Gut Microbial Community and Prevents Colonic Mucus Degradation in Mice with Colitis.

The role of dietary amino acids or intact proteins in the progression of colitis remains controversial, and the mechanism involving gut microbes is unclear. Here, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of dextran sulfate sodium (DSS)-induced colitis in mice. Our results showed that the ED induced remission of colitis in mice. Notably, ED treatment reduced the abundance of the mucolytic bacteria Akkermansia and Bacteroides, which was attributed to decreased colonic protein fermentation. Consistently, the activities of mucolytic enzymes were decreased, leading to protection against mucus layer degradation and microbial invasion. Fecal microbiota transplantation from ED-fed mice reshaped microbial ecology and alleviated intestinal inflammation in recipient mice. The ED failed to induce remission of colitis in pseudogermfree mice. Together, our results demonstrate the critical role of the gut microbiota in the prevention of colitis by an ED. IMPORTANCE The prevalence of inflammatory bowel disease is rapidly increasing and has become a global burden. Several specific amino acids have been shown to benefit mucosal healing and colitis remission. However, the role of amino acids or intact proteins in diets and enteral nutrition formulas is controversial, and the mechanisms involving gut microbes remain unclear. In this study, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of colitis in mice. The underlying mechanisms were explored by utilizing fecal microbiota transplantation and pseudogermfree mice. ED treatment reduced the abundance of mucolytic bacteria, thereby protecting the mucus layer from microbial invasion and degradation. For the first time, we convincingly demonstrated the critical role of gut microbiota in the effects of the ED. This study may provide new insights into the gut microbiota-diet interaction and its role in human health.

Restricting a single amino acid cross-protects Drosophila melanogaster from nicotine poisoning through mTORC1 and GCN2 signalling.

Dietary interventions that restrict protein intake have repeatedly been shown to offer beneficial health outcomes to the consumer. Benefits such as increased stress tolerance can be observed when individual amino acids are restricted, thus mimicking dietary protein restriction. Here, we sought to further understand the relationship between dietary amino acids and stress tolerance using Drosophila melanogaster. Using a chemically defined medium for Drosophila, we found that transiently restricting adult flies of a single essential amino acid generally protects against a lethal dose of the naturally occurring insecticide, nicotine. This protection varied with the identity of the focal amino acid and depended on the duration and intensity of its restriction. To understand the molecular basis of these effects, we modified the signalling of two cellular sensors of amino acids, GCN2 and mTORC1, in combination with amino acid restriction. We found that GCN2 was necessary for diets to protect against nicotine, whereas the suppression of mTORC1 was sufficient to induce nicotine resistance. This finding implies that amino acid restriction acts via amino acid signalling to cross-protect against seemingly unrelated stressors. Altogether, our study offers new insights into the physiological responses to restriction of individual amino acids that confer stress tolerance.

Potential benefits of amino acid supplementation for cervid performance and nutritional ecology, with special focus on lysine and methionine: A review.

Deer farming is a thriving industry for venison, velvet antlers, trophy hunting, and other by-products. Feeding and nutrition are important factors for improving production performance, especially dietary protein and amino acids (AAs), as they are the main components of all tissues. Only a few studies on AA supplementation (Lys, Met, Arg) have been performed on cervids, which show positive effects on weight gain, ADG, feed-:gain ratio, plasma AAs, carcass weight, dressing percentage, yield of high-quality muscles, storage of internal fat during winter, DM and CP digestibility, plasma protein- and fat-related metabolite concentrations, antler burr perimeter, weight, length and mineralisation, velvet antler yield, rumen volatile fatty acids, and microbiome composition. All these effects are relevant for supporting the production of cervids products, from venison to velvet or trophy antlers, as well as their general performance and well-being of captive-bred cervids. The current available information suggests that AA supplementation can be especially interesting for animals fed low protein rations, and growing animals, but should be avoided in high rations and during winter, since it may promote the accumulation of internal fat. Potential effects on milk production and the concentrations of different hormones involved in the regulation of the antler cycle should be further explored.

Feeding pigs amino acids as protein-bound or in free form influences postprandial concentrations of amino acids, metabolites, and insulin

Dietary proteins need to be digested first while free amino acids (AAs) and small peptides are readily available for absorption and rapidly appear in the blood. The rapid postprandial appearance of dietary AA in the systemic circulation may result in inefficient AA utilisation for protein synthesis of peripheral tissues if other nutrients implicated in AA and protein metabolism are not available at the same time. The objective of this experiment was to compare the postprandial concentrations of plasma AA and other metabolites after the ingestion of a diet that provided AA either as proteins or as free AA and small peptides. Twenty-four male growing pigs (38.8 ± 2.67 kg) fitted with a jugular catheter were assigned to one of three diets that provided AA either in protein form (INT), free AA and small peptides (HYD), or as free AA (FAA). After an overnight fast and initial blood sampling, a small meal was given to each pig followed by serial blood collection for 360 min. Postprandial concentrations of plasma AA, glucose, insulin, and urea were then measured from the collected blood. Non-linear regression was used to summarise the postprandial plasma AA kinetics. Fasting concentrations of urea and some AA were higher (P < 0.05) while postprandial plasma insulin and glucose were lower (P < 0.01) for INT than for HYD and FAA. The area under the curve of plasma concentration after meal distribution was lower for INT for most AAs (P < 0.05), resulting in a flatter curve compared to HYD and FAA. This was the result of the slower appearance of dietary AA in the plasma when proteins are fed instead of free AA and small peptides. The flatter curve may also result from more AAs being metabolised by the intestine and liver when INT was fed. The metabolism of AA of the intestine and liver was higher for HYD than FAA. Providing AA as proteins or as free AA and small peptides affected the postprandial plasma kinetics of AA, urea, insulin, and glucose. Whether the flat kinetics when feeding proteins has a positive or negative effect on AA metabolism still needs to be explored.

Nutritional management and branched-chain amino acids diet among patients undergoing living donor liver transplantation

Nutritional management and branched-chain amino acids diet among patients undergoing living donor liver transplantation

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.

Abstract 10708: Dietary Methionine Restriction Protects Against Abdominal Aortic Aneurysm via Amino Acid Starvation Response

Introduction: Dietary intervention emerges as a promising non-medicinal avenue for the treatment of a wide range of diseases. Limiting the intake of single amino acid has been shown to produce health benefits similar to that of calorie restriction yet without significant risks of malnutrition. One of the established regimen, methionine restriction (MR), was recently shown to confer pleiotropic benefits in cardiometabolic disease models, largely attributed to the activation of the GCN2-mediated amino acid starvation response pathway. However, the therapeutic and mechanistic implications of dietary amino acid restriction remain unknown in abdominal aortic aneurysm (AAA), a lethal vascular disease that is without a cure other than the traumatic surgical repairs. Herein, we sought to probe the outcome of MR as well as the role of GCN2 in AAA. Methods and Results: Following a 2-week pre-treatment with MR (20% methionine level) or iso-caloric control diet, male Sprague Dawley rats were subjected to intraluminal elastase perfusion. At day 7, animals in the MR group showed significantly less aneurysmal dilation in comparison to control. To investigate the contribution from the GCN2-mediated amino acid starvation response, we subjected animals to the same dietary regimen of MR or control, followed by GCN2 silencing in the elastase-challenged aortic segments through localized infusion with GCN2-targeting or scrambled shRNA lentivirus. Indeed, tuning down aortic GCN2 effectively compromised the benefits exerted by MR against AAA. Finally, we determined whether GCN2 constitutes an intrinsic protector against aortic degeneration using GCN2 knockout mice ( Gcn2 -/- ). Following periaortic elastase challenge and β-aminopropionitrile treatment, Gcn2 -/- mice displayed exacerbated expansion of aneurysmal lesions in comparison to Gcn2 +/+ control mice at day 28 post procedure. Conclusions: Our study provides the first experimental evidence supporting a potential role of dietary amino acid restriction (e.g., MR) in the prevention of AAA development. Additionally, GCN2-mediated amino acid starvation response possibly underlies the anti-AAA benefit exerted by MR and serves as an intrinsic protector against AAA pathogenesis.

Amino acid variability, tradeoffs and optimality in human diet

Studies at the molecular level demonstrate that dietary amino acid intake produces substantial effects on health and disease by modulating metabolism. However, how these effects may manifest in human food consumption and dietary patterns is unknown. Here, we develop a series of algorithms to map, characterize and model the landscape of amino acid content in human food, dietary patterns, and individual consumption including relations to health status, covering over 2,000 foods, ten dietary patterns, and over 30,000 dietary profiles. We find that the type of amino acids contained in foods and human consumption is highly dynamic with variability far exceeding that of fat and carbohydrate. Some amino acids positively associate with conditions such as obesity while others contained in the same food negatively link to disease. Using linear programming and machine learning, we show that these health trade-offs can be accounted for to satisfy biochemical constraints in food and human eating patterns to construct a Pareto front in dietary practice, a means of achieving optimality in the face of trade-offs that are commonly considered in economic and evolutionary theories. Thus this study may enable the design of human protein quality intake guidelines based on a quantitative framework.

Nutraceutical Approach to the Management of Cystic Fibrosis

Background: Cystic fibrosis (CF) is an autosomal recessive monogenic disease marked by a mutation in the cystic fibrosis transmembrane conductance regulator gene. Cystic fibrosis transmembrane conductance regulator gene mutations affect respiratory, digestive and reproductive functions and impede bicarbonate, bile acid, and sweat secretion. Moreover, the current trend indicates that CF is no longer only a paediatric disease, but has progressively become a disease that also affects adults. This calls for addressing the condition with an appropriate nutraceutical approach. Objective: The study aims to find and collate nutritional targets in the management of cystic fibrosis. Method: Studies highlighting the benefits of nutrients or nutraceuticals in the management of cystic fibrosis were included from previously published research articles (1971 to 2020). Data including nutrients, nutraceuticals, study design, study model, sample size, age, dose and duration of the dose of the supplement were extracted from the studies included and explored to understand their role. Results: About 26 studies were included in the present review. It was found that nutrient interventions comprising nutraceuticals, including dietary fibre, proteins and amino acids (taurine, arginine, glutathione), fats (medium-chain triglycerides, polyunsaturated fatty acids (omega-3 fatty acids), phytochemicals (apigenin, genistein, quercetin, curcumin, allicin, beta-carotene, Pulmonaria officinalis L, Epigallocatechin-3-gallate), micronutrients, including vitamin A, vitamin D, vitamin K, magnesium and zinc in addition to antioxidants exhibit improvement in the symptomatic condition of cystic fibrosis patients. Conclusion: The advent of nutraceuticals in the food industry and studies indicating their promising benefits have paved a path for targeted therapies in cystic fibrosis.

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss

Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics.

Investigating the Kidney-Gut-Brain Axis in CKD: Effects of High Amino Acids Diet With/Without Antibiotic Therapy

Investigating the Kidney-Gut-Brain Axis in CKD: Effects of High Amino Acids Diet With/Without Antibiotic Therapy

An oral gavage of lysine elicited early satiation while gavages of lysine, leucine, or isoleucine prolonged satiety in pigs.

Excess dietary amino acids (AA) may negatively affect feed intake in pigs. Previous results showed that Lys, Leu, Ile, Phe, and Glu significantly increased gut peptide secretion (i.e., cholecystokinin, glucagon-like peptide 1). However, the link between dietary AA and gut peptide secretion with changes in feeding behavior patterns has not been demonstrated to date in pigs. The aim of the present study was to determine the effect of Lys, Leu, Ile, Phe, and Glu, on feed intake and meal patterns in young pigs. Twelve male pigs (Landrace × Large White, body weight = 16.10 ± 2.69 kg) were administered an oral gavage of water (control) or Lys, Leu, Ile, Phe, Glu, or glucose (positive control) at 3 mmol.kg-1 following an overnight fasting. The experiment consisted in measuring individual feed disappearance and changes in meal pattern (including latency to first meal, first meal duration, intermeal interval, second meal duration, and number of meals) based on video footage. Compared to the control group Lys significantly (P ≤ 0.01) reduced feed intake during the first 30 min and up to 2.5 h post-gavage, including a reduction (P ≤ 0.05) in the first meal duration. Similarly, Leu and Ile also significantly decreased feed intake up to 3 h post-gavage on a cumulative count. However, the strongest (P ≤ 0.01) impacts on feed intake by the two branched chained AA were observed after the first- or second-hour post-gavage for Leu or Ile, respectively. In addition, Leu or Ile did not affect the first meal duration (P ≥ 0.05). Leu significantly increased (P ≤ 0.01) the intermeal interval while decreasing (P ≤ 0.05) the number of meals during the initial 2 h following the gavage when compared with the control group. In contrast, the oral gavages of Phe or Glu had no significant impact (P > 0.05) on the feeding behavior parameters measured relative to the control pigs. In turn, glucose had a short-lived effect on appetite by reducing (P < 0.05) feed intake for 30 min after the first-hour post-gavage. In conclusion, the impact of an oral gavage of Lys on feeding behavior is compatible with a stimulation of early satiation and an increased duration of satiety. The main impact of the oral gavages of Leu and Ile was an increase in the duration of satiety. The gastrointestinal mechanisms associated with non-bound dietary AA sensing and the impact on voluntary feed intake warrant further investigations.

Excretion of excess nitrogen and increased survival by loss of SLC6A19 in a mouse model of ornithine transcarbamylase deficiency.

Protein catabolism ultimately yields toxic ammonia, which must be converted to urea by the liver for renal excretion. In extrahepatic tissues, ammonia is temporarily converted primarily to glutamine for subsequent hepatic extraction. Urea cycle disorders (UCDs) are inborn errors of metabolism causing impaired ureagenesis, leading to neurotoxic accumulation of ammonia and brain glutamine. Treatment includes dietary protein restriction and oral "ammonia scavengers." These scavengers chemically combine with glutamine and glycine to yield excretable products, creating an alternate pathway of waste nitrogen disposal. The amino acid transporter SLC6A19 is responsible for >95% of absorption and reabsorption of free neutral amino acids in the small intestine and kidney, respectively. Genetic SLC6A19 deficiency causes massive neutral aminoaciduria but is typically benign. We hypothesized that inhibiting SLC6A19 would open a novel and effective alternate pathway of waste nitrogen disposal. To test this, we crossed SLC6A19 knockout (KO) mice with spfash mice, a model of ornithine transcarbamylase (OTC) deficiency. Loss of SLC6A19 in spfash mice normalized plasma ammonia and brain glutamine and increased median survival in response to a high protein diet from 7 to 97 days. While induced excretion of amino acid nitrogen is likely the primary therapeutic mechanism, reduced intestinal absorption of dietary free amino acids, and decreased muscle protein turnover due to loss of SLC6A19 may also play a role. In summary, the results suggest that SLC6A19 inhibition represents a promising approach to treating UCDs and related aminoacidopathies.

Protein Intake and Oral Health in Older Adults-A Narrative Review.

Oral health is vital to general health and well-being for all ages, and as with other chronic conditions, oral health problems increase with age. There is a bi-directional link between nutrition and oral health, in that nutrition affects the health of oral tissues and saliva, and the health of the mouth may affect the foods consumed. Evidence suggests that a healthy diet generally has a positive impact on oral health in older adults. Although studies examining the direct link between oral health and protein intake in older adults are limited, some have explored the relationship via malnutrition, which is also prevalent among older adults. Protein-energy malnutrition (PEM) may be associated with poor oral health, dental caries, enamel hypoplasia, and salivary gland atrophy. This narrative review presents the theoretical evidence on the impact of dietary protein and amino acid composition on oral health, and their combined impact on overall health in older adults.

The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (SLC38A3, SLC38A7 and SLC38A9) Affects Susceptibility to Type 2 Diabetes and Vascular Complications

Type 2 Diabetes (T2D) is a metabolic disease associated with long-term complications, with a multifactorial pathogenesis related to the interplay between genetic and modifiable risk factors, of which nutrition is the most relevant. In particular, the importance of proteins and constitutive amino acids (AAs) in disease susceptibility is emerging. The ability to sense and respond to changes in AA supplies is mediated by complex networks, of which AA transporters (AATs) are crucial components acting also as sensors of AA availability. This study explored the associations between polymorphisms in selected AATs genes and T2D and vascular complications in 433 patients and 506 healthy controls. Analyses revealed significant association of SLC38A3-rs1858828 with disease risk. Stratification of patients based on presence/absence of vascular complications highlighted significant associations of SLC7A8-rs3783436 and SLC38A7-rs9806843 with diabetic retinopathy. Additionally, the SLC38A9-rs4865615 resulted associated with chronic kidney disease. Notably, these genes function as AAs sensors, specifically glutamine, leucine, and arginine, linked to the main nutrient signaling pathway mammalian target of rapamycin complex 1 (mTORC1). Thus, their genetic variability may contribute to T2D by influencing the ability to properly transduce a signal activating mTORC1 in response to AA availability. In this scenario, the contribution of dietary AAs supply to disease risk may be relevant.

The association between dietary branched-chain amino acids and the risk of cardiovascular diseases in Chinese patients with type 2 diabetes: A hospital-based case-control study.

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 <0.001 for total BCAA; OR Q4−Q1 = 0.20, 95%CI = 0.07, 0.53, P trend = 0.001 for leucine). For each 1-S.D. increase in total dietary BCAA, leucine or valine intake was associated with 54% (95%CI = 29%, 70%, P = 0.001), 64% (95%CI = 29%, 82%, P = 0.003), or 54% (95%CI = 1%, 79%, P = 0.049) decrease in the risk of CVD, respectively. Whole grains, starchy vegetables, mushrooms, fruit, eggs, and dairy and dairy product-derived BCAA were found to attenuate CVD risk (P ranged: = 0.002–0.027).ConclusionHigher BCAA intake, in particular leucine and valine, might be associated with a lower risk of CVD.

Postprandial plasma amino acid and metabolite kinetics of adult and growing pigs fed a diet with a balanced or unbalanced amino acid profile

Feeding diets with an unbalanced amino acid (AA) profile can reduce the postprandial AA utilization for protein synthesis. Growing pigs use dietary AA mainly for protein accretion, whereas non-lactating and non-pregnant adult pigs use AA mainly for maintenance. The requirement for AA for growth is much larger than that for maintenance and growing pigs may therefore be more affected by a diet with an unbalanced AA profile than adult pigs. This study aimed to compare the postprandial plasma AA and metabolite concentrations of adult and growing pigs after feeding a diet with either an unbalanced (UNB) or a balanced AA profile (BAL). The postprandial plasma concentrations of AA were used to study the influence of AA balance on postprandial AA metabolism. Extensively hydrolysed feathers (EHF) were used as an AA source. Both BAL and UNB contained EHF supplemented with L-Ala, L-Asp, L-Glu, Gly, and L-Trp while BAL was also supplemented with L-His, L-Ile, L-Lys, L-Met, and L-Tyr. Four growing and four male adult pigs were fitted with a jugular catheter and received each diet as a meal test thrice. The meal test consisted of giving a small meal after an overnight fast followed by serial blood collection for 360 min. A non-linear regression model was used to describe the postprandial plasma AA kinetics. Plasma kinetics of adult and growing pigs fed BAL resulted in a higher area under the curve (AUC) for the AA that were used to balance the diet. For the other AA, feeding BAL resulted in lower AUC, suggesting faster metabolic utilization of AA for protein synthesis. The apparent quantity of dietary AA appearing in the plasma after feeding was lower in adult pigs, suggesting higher first-pass AA utilization in the intestine and liver. For adult and growing pigs, balancing the AA profile of the diet resulted in faster overall metabolic utilization of AA as seen in the generally lower AUC of BAL compared to UNB.

Effects of dietary branched-chain amino acid supplementation on serum and milk metabolome profiles in dairy cows during early lactation.

The 3 branched-chain AA (BCAA), Val, Leu, and Ile, are essential AA used by tissues as substrates for protein synthesis and energy generation. In addition, BCAA are also involved in modulating cell signaling pathways, such as nutrient sensing and insulin signaling. In our previous study, dietary BCAA supplementation was shown to improve protein synthesis and glucose homeostasis in transition cows. However, a more detailed understanding of the changes in metabolic pathways associated with an increased BCAA availability is desired to fine-tune nutritional supplementation strategies. Multiparous Holstein cows (n = 20) were enrolled 28 d before expected calving and assigned to either the BCAA treatment (n = 10) or the control group (n = 10). Cows assigned to BCAA were fed 550 g/d of rumen-protected BCAA mixed with 200 g/d of dry molasses from calving until 35 DIM, whereas the cows assigned to the control were fed only 200 g/d of dry molasses. Serum samples were collected on d 10 before expected calving, as well as on d 4 and d 21 postpartum. Milk samples were collected on d 14 postpartum. From a larger cohort, we selected 20 BCAA-supplemented cows with the greatest plasma urea nitrogen concentration, as an indicator for greater BCAA availability, for the metabolomics analysis herein. Serum and milk samples were subjected to a liquid chromatography-mass spectrometry-based assay, detecting and measuring the abundance of 241 serum and 211 milk metabolic features, respectively. Multivariable statistical analyses revealed that BCAA supplementation altered the metabolome profiles of both serum and milk samples. Increased abundance of serum phosphocholine and glutathione and of milk Val, Ile, and Leu, and decreased abundance of milk acyl-carnitines were associated with BCAA supplementation. Altered phosphocholine and glutathione abundances point to altered hepatic choline metabolism and antioxidant balance, respectively. Altered milk acyl-carnitine abundances suggest changes in mammary fatty acid metabolism. Dietary BCAA supplementation was associated with a range of alterations in serum and milk metabolome profiles, adding to our understanding of the role of BCAA availability in modulating dairy cow protein, lipid, and energy metabolism on a whole-body level and how it affects milk composition.