Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves

The effects of different amino acid (AA) supplementations of milk protein-based milk replacers in pre-ruminant calves from 3 days to 7 weeks of age were studied. Animals were divided into 4 groups: Ctrl) Control group fed with milk protein-based milk replacer without supplementation; GP) supplementation with 0.1% glycine and 0.3% proline; FY) supplementation with 0.2% phenylalanine and 0.2% tyrosine; MKT) supplementation with 0.62% lysine, 0.22% methionine and 0.61% threonine. For statistical analysis, t-test was used to compare AA-supplemented animals to the Ctrl group. At week 7, body weight and average daily gain (ADG) were measured and blood samples and skeletal muscle biopsies were taken. Blood biochemistry analytes related to energy metabolism were determined and it was shown that MKT group had higher serum creatinine and higher plasma concentration of three supplemented AAs as well as arginine compared with the Ctrl group. GP group had similar glycine/proline plasma concentration compared with the other groups while in FY group only plasma phenylalanine concentration was higher compared with Control. Although the AA supplementations in the GP and FY groups did not affect average daily gain and metabolic health profile from serum, the metabolome analysis from skeletal muscle biopsy revealed several differences between the GP-FY groups and the Ctrl-MKT groups, suggesting a metabolic adaptation especially in GP and FY groupsinfo:eu-repo/semantics/publishedVersio

An Observational Cohort Study of the Kynurenine to Tryptophan Ratio in Sepsis: Association with Impaired Immune and Microvascular Function

Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-γ, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma amino acids were measured by high performance liquid chromatography and microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio was increased in sepsis (median 141 [IQR 64–235]) compared to controls (36 [28–52]); p<0.0001), and correlated with plasma interferon-γ and interleukin-10, and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic blood pressure and microvascular reactivity. In response to treatment of severe sepsis, the median KT ratio decreased from 162 [IQR 100–286] on day 0 to 89 [65–139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO-mediated tryptophan catabolism is associated with dysregulated immune responses and impaired microvascular reactivity in sepsis and may link these two fundamental processes in sepsis pathophysiology

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial

BACKGROUND & AIMS: The requirement of leucine and essential amino acids (EAA) to stimulate muscle protein synthesis increases with age. To target muscle anabolism it is suggested that higher postprandial blood levels of leucine and EAA are needed in older people. The aim was to evaluate the impact of oral nutritional supplements with distinct protein source and energy density, resembling mixed meals, on serum amino acid profiles and on gastrointestinal behaviour. METHODS: Four iso-nitrogenous protein (21 g) supplements were studied containing leucine-enriched whey protein with 150/320 kcal (W150/W320) or casein protein with 150/320 kcal (C150/C320); all products contained carbohydrates (10 or 32 g) and fat (3 or 12 g). Postprandial serum AA profiles were evaluated in twelve healthy, older subjects who participated in a randomized, controlled, single blind, cross-over study. Gastrointestinal behaviour was studied in vitro by looking at gastric coagulation and cumulative intestinal protein digestion over time. RESULTS: The peak serum leucine concentration was twofold higher for W150 vs. C150 (521 +/- 15 vs. 260 +/- 15 mumol/L, p < 0.001), higher for W320 vs. C320 (406 +/- 15 vs. 228 +/- 15 mumol/L, p < 0.001), and higher for low-caloric vs. high-caloric products (p < 0.001 for pooled analyses; p < 0.001 for interaction protein source*caloric density). Similar effects were observed for the peak concentrations of EAA and total AA (TAA). In vitro gastric coagulation was observed only for the casein protein supplements. Intestinal digestion for 90 min resulted in higher levels of free TAA, EAA, and leucine for W150 vs. C150, for W150 vs. W320, and for C150 vs. C320 (p < 0.0125). CONCLUSIONS: A low caloric leucine-enriched whey protein nutritional supplement provides a higher rise in serum levels of TAA, EAA and leucine compared to casein protein or high caloric products in healthy, elderly subjects. These differences appear to be mediated in part by the gastrointestinal behaviour of these products. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02013466

Differential metabolic effects of casein and soy protein meals on skeletal muscle in healthy volunteers.

BACKGROUND & AIMS: Dietary protein intake is known to affect whole body and interorgan protein turnover. We examined if moderate-nitrogen and carbohydrate casein and soy meals have a different effect on skeletal muscle protein and amino acid kinetics in healthy young subjects. METHODS: Muscle protein and amino acid kinetics were measured in the postabsorptive state and during 4-h enteral intake of isonitrogenous [0.21 g protein/(kg body weight. 4 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope and muscle biopsy techniques were used to study metabolic effects. RESULTS: The net uptake of glutamate, serine, histidine, and lysine across the leg was larger during CAPM than during SOPM intake. Muscle concentrations of glutamate, serine, histidine, glutamine, isoleucine and BCAA changed differently after CAPM and SOPM (P < 0.05). Muscle net protein breakdown decreased significantly (P < 0.05) to zero during feeding of both CAPM and SOPM, but differences in their (net) breakdown rates were not significant. Muscle protein synthesis was not different between CAPM and SOPM. CONCLUSION: Moderate-nitrogen casein and soy protein meals differently alter leg amino acid uptake without a significant difference in influencing acute muscle protein metabolism

Low Levels of Branched Chain Amino Acids, Eicosapentaenoic Acid and Micronutrients are Associated with Low Muscle Mass, Strength and Function in Community-Dwelling Older Adults

Low Levels of Branched Chain Amino Acids, Eicosapentaenoic Acid and Micronutrients are Associated with Low Muscle Mass, Strength and Function in Community-Dwelling Older Adult

Do malnutrition, sarcopenia and frailty overlap in nursing-home residents?

Objectives: To study the prevalence and overlap between malnutrition, sarcopenia and frailty in a selected group of nursing home (NH) residents. Design Cross-sectional descriptive study. Setting: Nursing homes (NH). Participants: 92 residents taking part in an exercise and oral nutritional supplementation study; &gt;75 years old, able to rise from a seated position, body mass index &lt;= 30 kg/m(2)and not receiving protein-rich oral nutritional supplements. Measurements: The MNA-SF and Global Leadership Initiative on Malnutrition (GLIM) criteria were used for screening and diagnosis of malnutrition (moderate or severe), respectively. Sarcopenia risk was assessed by the SARC-F Questionnaire (0-10p; &gt;= 4=increased risk), and for diagnosis the European Working Group of Sarcopenia in Older People (EWGSOP2) criteria was used. To screen for frailty the FRAIL Questionnaire (0-5p; 1-2p indicating pre-frailty, and &gt;3p indicating frailty), was employed. Results: Average age was 86 years; 62% were women. MNA-SF showed that 30 (33%) people were at risk or malnourished. The GLIM criteria verified malnutrition in 16 (17%) subjects. One third (n=33) was at risk for sarcopenia by SARC-F. Twenty-seven (29%) subjects displayed confirmed sarcopenic according to EWGSOP2. Around 50% (n=47) was assessed as pre-frail or frail. Six people (7%) suffered from all three conditions. Another five (5%) of the residents were simultaneously malnourished and sarcopenic, but not frail, while frailty coexisted with sarcopenia in 10% (n=9) of non-malnourished residents. Twenty-nine (32%) residents were neither malnourished, sarcopenic nor frail. Conclusions: In a group of selected NH residents a majority was either (pre) frail (51%), sarcopenic (29%) or malnourished (17%). There were considerable overlaps between the three conditions