Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals

Desine, Stacy; Gabriel, Curtis L.; Smith, Holly M.; Antonetti, Olivia R.; Wang, Chuan; Calcutt, M. Wade; Doran, Amanda C.; Silver, Heidi J.; Nair, Sangeeta; Terry, James G.; Carr, John Jeffrey; Linton, MacRae F.; Brown, Jonathan D.; Koethe, John R.; Ferguson, Jane F.

doi:10.3389/fendo.2023.1122391

Cited by 3 publications

(2 citation statements)

References 49 publications

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“…At the metabolite level, we observed elevated levels of serum branched chained amino acids, α-AAA, urinary 4-deoxyerythronic acid, 3-hydroxisobutyrate, and dysregulation in diacyl chain phosphatidylcholines associated with prenatal metals and persistent chemicals mixtures and increased MetS score. Branched chained amino acids, well-known regulators of glucose and lipid metabolism, and α-AAA have been shown to be associated with MetS risk components in healthy adults before disease onset . Consistently, 4-deoxyerythronic levels were associated with a higher BMI in childhood in the HELIX study .…”

Section: Discussionmentioning

confidence: 69%

“…Branched chained amino acids, well-known regulators of glucose and lipid metabolism, 64 and α-AAA have been shown to be associated with MetS risk components in healthy adults before disease onset. [65][66][67][68] Consistently, 4-deoxyerythronic levels were associated with a higher BMI in childhood in the HELIX study. 69 3-Hydroxyisobutyrate, whose fermentation by gut bacteria may lead to the production of short-chain fatty acids regulating overall metabolic activity, 70 has also been associated with to obesity, insulin resistance, and T2D.…”

Section: Jama Network Open | Environmental Healthmentioning

confidence: 64%

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Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children

Güil-Oumrait,

Stratakis,

Maitre

et al. 2024

JAMA Netw Open

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ImportancePrenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied chemical mixtures or explored underlying protein and metabolic signatures.ObjectiveTo investigate associations of prenatal exposure to EDC mixtures with MetS risk score in children and identify associated proteins and metabolites.Design, Setting, and ParticipantsThis population-based, birth cohort study used data collected between April 1, 2003, and February 26, 2016, from the Human Early Life Exposome cohort based in France, Greece, Lithuania, Norway, Spain, and the UK. Eligible participants included mother-child pairs with measured prenatal EDC exposures and complete data on childhood MetS risk factors, proteins, and metabolites. Data were analyzed between October 2022 and July 2023.ExposuresNine metals, 3 organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 5 perfluoroalkyl substances (PFAS), 10 phthalate metabolites, 3 phenols, 4 parabens, and 4 organophosphate pesticide metabolites measured in urine and blood samples collected during pregnancy.Main Outcomes and MeasuresAt 6 to 11 years of age, a composite MetS risk score was constructed using z scores of waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Childhood levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were quantified using targeted methods. Associations were assessed using bayesian weighted quantile sum regressions applied to mixtures for each chemical group.ResultsThe study included 1134 mothers (mean [SD] age at birth, 30.7 [4.9] years) and their children (mean [SD] age, 7.8 [1.5] years; 617 male children [54.4%] and 517 female children [45.6%]; mean [SD] MetS risk score, −0.1 [2.3]). MetS score increased per 1-quartile increase of the mixture for metals (β = 0.44; 95% credible interval [CrI], 0.30 to 0.59), organochlorine pesticides (β = 0.22; 95% CrI, 0.15 to 0.29), PBDEs (β = 0.17; 95% CrI, 0.06 to 0.27), and PFAS (β = 0.19; 95% CrI, 0.14 to 0.24). High-molecular weight phthalate mixtures (β = −0.07; 95% CrI, −0.10 to −0.04) and low-molecular weight phthalate mixtures (β = −0.13; 95% CrI, −0.18 to −0.08) were associated with a decreased MetS score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were associated with increased MetS score.Conclusions and RelevanceThis cohort study suggests that prenatal exposure to EDC mixtures may be associated with adverse metabolic health in children. Given the pervasive nature of EDCs and the increase in MetS, these findings hold substantial public health implications.

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Section: Discussionmentioning

confidence: 69%

Section: Jama Network Open | Environmental Healthmentioning

confidence: 64%

Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children

Güil-Oumrait,

Stratakis,

Maitre

et al. 2024

JAMA Netw Open

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Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus

Freiberg,

Reyes Ruiz,

Gimza

et al. 2024

Nat Commun

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Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S. aureus infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-staphylococcal antibiotics are examined using both quantitative proteomics and transposon sequencing. These screens indicate that arginine metabolism is involved in antibiotic tolerance within a biofilm and support the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH , the final gene in the arginine synthesis pathway, induces antibiotic tolerance. Arginine restriction induces antibiotic tolerance via inhibition of protein synthesis. In murine skin and bone infection models, an argH mutant has enhanced ability to survive antibiotic treatment with vancomycin, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.

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Comparative Analysis of Serum Amino Acid Profiles in Patients with Myasthenia Gravis and Multiple Sclerosis

Kośliński,

Rzepiński,

Koba

et al. 2024

JCM

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Background: Multiple sclerosis (MS) and myasthenia gravis (MG) are autoimmune diseases that attack the central nervous system (CNS) and the neuromuscular junction, respectively. As the common pathogenesis of both diseases is associated with an autoimmune background and the involvement of T and B lymphocytes, the overlapping of selected clinical symptoms may cause difficulties in the differential diagnosis of both diseases. Methods: The aim of the study was to use Liquid Chromatography–Electrospray Ionization–Mass Spectrometry (LC–ESI–MS/MS) in conjunction with multivariate statistical analyses to examine the changes in amino acid metabolic profiles between patients with MG, MS, and a control group. Results: Comparative analysis of amino acids (AA) between patients with MG, MS, and within the control group allowed for the identification of statistically significant differences in the amino acid profile. Comparing the patients (patients with MS and MG) with the control group, and after taking the results of multiple tests into account, it was observed that amino acids such as ARG, PRO, TRP, CIT were significantly different between the groups. When considering the comparison between the AA concentrations in MS and MG patients, we found three AAs that were significantly different in the MS and MG groups, after correcting for multiple testing (CIT, GABA, and AAA). Higher concentrations of amino acids that showed significant differences were observed in patients with myasthenia gravis. Conclusions: Our results have indicated AAs that may prove valuable for improving the diagnostics of MS and MG patients. To better assess the potential utility of these markers, their performance requires further validation in a larger study group and limitation of possible confounding factors, e.g., medications and diet.

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Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals

Cited by 3 publications

References 49 publications

Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children

Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children

Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus

Comparative Analysis of Serum Amino Acid Profiles in Patients with Myasthenia Gravis and Multiple Sclerosis

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