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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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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.