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1.
Beneficial effects of whole-body cryotherapy on glucose homeostasis and amino acid profile are associated with a reduced myostatin serum concentration.
Kozłowska, M, Kortas, J, Żychowska, M, Antosiewicz, J, Żuczek, K, Perego, S, Lombardi, G, Ziemann, E
Scientific reports. 2021;(1):7097
Abstract
The study investigated the effect of single and chronic (10 sessions) whole-body cryotherapy (WBC; 3-min, - 110 °C) on amino acid (AA) profile, myostatin, fibroblast growth factor 21 (FGF21), and concentrations of brain-derived neurotrophic factor (BDNF), irisin and adiponectin in relation to glucose homeostasis. Thirty-five, healthy men were randomly split into experimental (young: 28 ± 7 years and middle-aged: 51 ± 3 years) and control groups. Blood samples were taken before and 1 h after the first and last (10th) WBC session. Baseline myostatin correlated significantly with visceral fat area, glucose, insulin, HOMA-IR and irisin (all p < 0.05). The single session of WBC induced temporary changes in AA profile, whereas chronic exposure lowered valine and asparagine concentrations (p < 0.01 and p = 0.01, respectively) compared to the baseline. The chronic WBC reduced fasting glucose (p = 0.04), FGF21 (- 35.8%, p = 0.06) and myostatin (-18.2%, p = 0.06). Still, the effects were age-dependent. The decrease of myostatin was more pronounced in middle-aged participants (p < 0.01). Concentrations of irisin and adiponectin increased in response to chronic WBC, while BDNF level remained unchanged. By improving the adipo-myokine profile, chronic WBC may reduce effectively the risk of the metabolic syndrome associated with hyperinsulinemia, increased levels of valine and asparagine, and muscle atrophy.
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Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests.
Masoodi, M, Gastaldelli, A, Hyötyläinen, T, Arretxe, E, Alonso, C, Gaggini, M, Brosnan, J, Anstee, QM, Millet, O, Ortiz, P, et al
Nature reviews. Gastroenterology & hepatology. 2021;(12):835-856
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and is often associated with aspects of metabolic syndrome. Despite its prevalence and the importance of early diagnosis, there is a lack of robustly validated biomarkers for diagnosis, prognosis and monitoring of disease progression in response to a given treatment. In this Review, we provide an overview of the contribution of metabolomics and lipidomics in clinical studies to identify biomarkers associated with NAFLD and nonalcoholic steatohepatitis (NASH). In addition, we highlight the key metabolic pathways in NAFLD and NASH that have been identified by metabolomics and lipidomics approaches and could potentially be used as biomarkers for non-invasive diagnostic tests. Overall, the studies demonstrated alterations in amino acid metabolism and several aspects of lipid metabolism including circulating fatty acids, triglycerides, phospholipids and bile acids. Although we report several studies that identified potential biomarkers, few have been validated.
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Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects.
Piro, MC, Tesauro, M, Lena, AM, Gentileschi, P, Sica, G, Rodia, G, Annicchiarico-Petruzzelli, M, Rovella, V, Cardillo, C, Melino, G, et al
Amino acids. 2020;(8):1125-1137
Abstract
Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome.
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4.
Are dietary amino acids prospectively predicts changes in serum lipid profile?
Teymoori, F, Asghari, G, Salehi, P, Sadeghian, S, Mirmiran, P, Azizi, F
Diabetes & metabolic syndrome. 2019;(3):1837-1843
Abstract
BACKGROUND Besides of dietary fat and carbohydrate, amino acids(AAs), as constituent components of dietary protein have been related with serum lipid levels. This study aims to examine the association between dietary AAs and prospective changes in serum lipid profile in adults. METHODS Analyses were conducted on 3881 participants aged, 18-75 years of Tehran lipid and Glucose study, at baseline (2008-2011) and were followed for 3 years (2011-2014) to ascertain serum lipid profile changes. Dietary intakes of AAs were collected at baseline using food frequency questionnaire. Multiple linear regression adjusted for age, sex, body mass index, physical activity, smoking and daily intakes of energy, total fat, and fiber were used. RESULTS The median(IQR) changes in triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were 6.0(-19.0, -35.5), 9.0(7.0, -24.0), 1.0(-3.0, -6.0), and 5.2(-8.0, -18.6) mg/dl, respectively. Higher intakes of isoleucine, lysine, tyrosine, alanine, threonine, methionine, valine, histidine, aspartic acid, and branched chain, alkaline, and alcoholic AAs were positively associated with TGs-changes in the final adjusted model, whereas tryptophan, glutamic acid, and acidic AAs were negatively related to TG-changes. Alanine and tryptophan were associated with higher and lower LDL-C-changes, respectively. Lysine, alanine, methionine, aspartic acid, and alkaline AAs showed positive association with changes in TC, whereas tryptophan and glutamic acid had a negative association with TC-changes. CONCLUSION Our findings showed that some dietary amino acids have the potential to increase or decrease serum lipid profile.
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Reduced Plasma Amino Acid Levels During Allogeneic Hematopoietic Stem Cell Transplantation Are Associated with Systemic Inflammation and Treatment-Related Complications.
Weischendorff, S, Kielsen, K, Nederby, M, Schmidt, L, Burrin, D, Heilmann, C, Ifversen, M, Sengeløv, H, Mølgaard, C, Müller, K
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019;(7):1432-1440
Abstract
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged by cytotoxic effects of the conditioning regimen, resulting in tissue damage, systemic inflammation, and increased metabolic demands for amino acids to regenerate damaged tissues, reconstitute hematopoietic cells, and establish antioxidant defenses. To date, few studies have addressed the role of plasma amino acid (PAA) levels during transplantation, and it remains unknown if amino acid deficiency can aggravate treatment-related morbidity. We determined plasma levels of the 23 human amino acids in 80 HSCT recipients (age 1.1 to 55.4 years) before conditioning and on days +7 and +21 post-transplant along with C-reactive protein (CRP) and IL-6 levels on day +7. Significant changes were observed in plasma concentrations of several human amino acids during HSCT. On day +7, numerous amino acids were inversely correlated with both CRP and IL-6, including glutamic acid, serine, alanine, glutamine, arginine, cysteine, glycine, histidine, lysine, tryptophan, threonine, taurine, proline, and methionine (r = -.22 to -.66; all P < .05). Patients who developed sinusoidal obstruction syndrome (SOS) had significantly lower mean total PAA levels compared with patients without SOS (2013 ng/L [95% confidence interval (CI), 1709 to 2318 ng/L] versus 2706 ng/L [95% CI, 2261 to 3150 ng/L]; P = .006), along with lower individual levels of glutamic acid, serine, arginine, glycine, lysine, valine, tryptophan, threonine, and proline on day +7 (all P < .05). Patients with severe acute graft-versus-host disease had a lower mean total PAA level (1922 ng/L [95% CI, 1738 to 2106 ng/L] versus 2649 ng/L [95% CI, 2244 to 3055 ng/L]; P = .014) and lower levels of serine, glutamine, cysteine, glycine, lysine, and threonine on day +7 (all P < .05). These results indicate a relationship between low concentrations of certain amino acids and the risk of treatment-related complications.
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Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.
Spanaki, AM, Tavladaki, T, Dimitriou, H, Kozlov, AV, Duvigneau, JC, Meleti, E, Weidinger, A, Papakonstantinou, E, Briassoulis, G
JPEN. Journal of parenteral and enteral nutrition. 2018;(6):1061-1074
Abstract
BACKGROUND Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. RESULTS Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (p<0.05); mHSP72, nHSP72, VO2 , VCO2 , EE, and metabolic pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently associated with sepsis, along with mHSP72 and eHSP90α (p<0.05); TBARS and VO2 were independently associated with organ failure (p<0.05)). Septic nonsurvivors had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin and adiponectin (p<0.05). CONCLUSIONS A pattern of early longitudinal induction of metabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome.
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Abnormal circulating amino acid profiles in multiple metabolic disorders.
Okekunle, AP, Li, Y, Liu, L, Du, S, Wu, X, Chen, Y, Li, Y, Qi, J, Sun, C, Feng, R
Diabetes research and clinical practice. 2017;:45-58
Abstract
AIM: To evaluate circulating amino acids (AA) profiles in obesity, type 2 diabetes (T2D) and metabolic syndrome (MetS). METHODS Serum AA were profiled among 200; healthy, obese, T2D and MetS subjects matched by sex, age and BMI using ultra-high performance liquid chromatography tandem quadruple mass spectrometry (UPLC-TQ-MS). A meta-analysis, including 47 case-control studies (including the current study) on serum AA in obesity, T2D and MetS searched through October 2016 was conducted to explore the AA differences in obesity, T2D and MetS. RESULTS In comparison with healthy controls, 14 AA (10 increased and 4 decreased) were significantly altered (P<0.05) in all non-healthy subjects. Also, mean differences of valine (obese: 34.13 [27.70, 40.56]µmol/L, P<0.001, T2D: 19.49 [3.31, 35.68]µmol/L, P<0.05, MetS: 29.18 [16.04, 42.33]µmol/L, P<0.001), glutamic acid (obese: 18.62 [11.64, 25.61]µmol/L, P<0.001, T2D: 19.94 [0.28, 39.61]µmol/L, P<0.05, MetS: 12.45 [3.98, 20.91]µmol/L, P<0.001), proline (obese: 16.72 [6.20, 27.24]µmol/L, P<0.001, T2D: 20.72 [15.82, 25.61]µmol/L, P<0.001, MetS: 29.95 [25.18, 34.71]µmol/L, P<0.001) and isoleucine (obese: 11.39 [8.54, 14.24]µmol/L, P<0.001, T2D: 7.37 [1.52, 13.22]µmol/L, P<0.05, MetS: 10.40 [4.90, 15.89]µmol/L, P<0.001) were significantly higher compared to healthy controls. Similarly, mean differences of glycine (obese: -30.99 [-39.69, -22.29]µmol/L, P<0.001, T2D: -30.37 [-41.80, -18.94]µmol/L, P<0.001 and MetS: -35.24 [-39.28, -31.21]µmol/L, P<0.001) were significantly lower compared to healthy controls. CONCLUSION In both the case-control study and meta-analysis, obesity was related to the most circulating AA changes, followed by MetS and T2D. Valine, isoleucine, glutamic acid and proline increased, while Glycine decreased in all metabolic disorders.
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Specific plasma amino acid disturbances associated with metabolic syndrome.
Siomkajło, M, Rybka, J, Mierzchała-Pasierb, M, Gamian, A, Stankiewicz-Olczyk, J, Bolanowski, M, Daroszewski, J
Endocrine. 2017;(3):553-562
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Abstract
PURPOSE The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process. METHODS Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(-): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed. The ability of the BCAA and AAA to discriminate subjects with MS and insulin resistance was tested. Based on logistic discrimination, a multivariate early MS diagnostic model was built, and its discrimination properties were evaluated. RESULTS Two functionally independent amino acid clusters were identified. BCAA and phenylalanine differed significantly between MS(+) and MS(-) participants (P = 0.003). These factors were also found to be indicators of MS(+) individuals (AUC: 0.66; 95% CI: 0.5757-0.7469), and correlated with cardiometabolic factors. No statistically significant differences in amino acid concentrations between those with and without insulin resistance were noted, and none of the amino groups were indicators of insulin resistance. The proposed MS multivariate diagnostic model consisted of phenylalanine, insulin, leptin, and adiponectin, and had good discrimination properties [AUC 0.79; 95% CI: 0.7239-0.8646]. CONCLUSIONS MS is associated with selective BCAA and AAA profile disturbances, which could be part of cardiometabolic disease pathogenesis and derive neither directly from insulin sensitivity impairment, nor obesity or muscle mass. The MS diagnostic model developed and described herein should be validated in future studies.
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Weight loss is associated with plasma free amino acid alterations in subjects with metabolic syndrome.
Tochikubo, O, Nakamura, H, Jinzu, H, Nagao, K, Yoshida, H, Kageyama, N, Miyano, H
Nutrition & diabetes. 2016;(2):e197
Abstract
OBJECTIVES The prevalence of metabolic syndrome is increasing worldwide, especially in Asian populations. Early detection and effective intervention are vital. Plasma free amino acid profile is a potential biomarker for the early detection for lifestyle-related diseases. However, little is known about whether the altered plasma free amino acid profiles in subjects with metabolic syndrome are related to the effectiveness of dietary and exercise interventions. METHODS Eighty-five Japanese subjects who fulfilled the Japanese diagnostic criteria for metabolic syndrome were enrolled in a 3-month diet and exercise intervention. The plasma free amino acid concentrations and metabolic variables were measured, and the relationships between plasma free amino acid profiles, metabolic variables and the extent of body weight reduction were investigated. Those who lost more than 3% of body weight were compared with those who lost less than 3%. RESULTS Baseline levels of most amino acids in the subset that went on to lose <3% body weight were markedly lower compared with the counterpart, although both groups showed similar proportional pattern of plasma amino acid profiles. The weight loss induced by the diet and exercise intervention normalized plasma free amino acid profiles. For those with a high degree of weight loss, those changes were also associated with improvement in blood pressure, triglyceride and hemoglobin A1c levels. CONCLUSIONS These data suggest that among Japanese adults meeting the criteria for metabolic syndrome, baseline plasma free amino acid profiles may differ in ways that predict who will be more vs less beneficially responsive to a standard diet and exercise program. Plasma free amino acid profiles may also be useful as markers for monitoring the risks of developing lifestyle-related diseases and measuring improvement in physiological states.
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[Can Plasma Free Amino Acid Profiling Be Used to Assess Cancer Risk?].
Ando, T
Rinsho byori. The Japanese journal of clinical pathology. 2016;(10):1163-1170
Abstract
Amino acids are present in the blood. In healthy people, the concentrations of these amino acids in the blood are maintained at stable levels. However, different diseases disturb the balance of amino acids in the blood in different ways. AminoIndex® is a service that uses the latest medical technology to measure the concentration of amino acids in the blood to check a person's health and detect various diseases. It is now possible to conduct an AminoIndex® Cancer Screening (AICS®) test that can detect cancer from early stages. The AICS® measures the concentrations of amino acids in the blood and statistically analyzes the differ- ences in the balance of amino acid concentrations between healthy people and those with cancer. As a result, we can simultaneously screen for certain types of cancer. Currently, the test can screen for gastric cancer, lung cancer, colorectal cancer, prostate cancer (in males), breast cancer (in females), and uterine/ovarian cancer* (in females). The application of AminoIndex® technology will spread through the fields of medicine, such as in the treat- ment of metabolic syndrome. (*The uterine/ovarian cancer test determines the overall risk of having any of the three cancers: cervical cancer, endometrial cancer, and ovarian cancer, and can not determine the individual risk of having each cancer.) [Review].