Browsing by Subject "Acylcarnitines"

Now showing 1 - 2 of 2
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    Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease
    (Wiley, 2022) Horgusluoglu, Emrin; Neff, Ryan; Song, Won-Min; Wang, Minghui; Wang, Qian; Arnold, Matthias; Krumsiek, Jan; Galindo-Prieto, Beatriz; Ming, Chen; Nho, Kwangsik; Kastenmüller, Gabi; Han, Xianlin; Baillie, Rebecca; Zeng, Qi; Andrews, Shea; Cheng, Haoxiang; Hao, Ke; Goate, Alison; Bennett, David A.; Saykin, Andrew J.; Kaddurah-Daouk, Rima; Zhang, Bin; Alzheimer's Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Metabolomics Consortium; Radiology and Imaging Sciences, School of Medicine
    Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and the pathogenesis of AD are poorly understood. In this study, we aim to identify AD‐specific metabolomic changes and their potential upstream genetic and transcriptional regulators through an integrative systems biology framework for analyzing genetic, transcriptomic, metabolomic, and proteomic data in AD. Metabolite co‐expression network analysis of the blood metabolomic data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) shows short‐chain acylcarnitines/amino acids and medium/long‐chain acylcarnitines are most associated with AD clinical outcomes, including episodic memory scores and disease severity. Integration of the gene expression data in both the blood from the ADNI and the brain from the Accelerating Medicines Partnership Alzheimer's Disease (AMP‐AD) program reveals ABCA1 and CPT1A are involved in the regulation of acylcarnitines and amino acids in AD. Gene co‐expression network analysis of the AMP‐AD brain RNA‐seq data suggests the CPT1A‐ and ABCA1‐centered subnetworks are associated with neuronal system and immune response, respectively. Increased ABCA1 gene expression and adiponectin protein, a regulator of ABCA1, correspond to decreased short‐chain acylcarnitines and amines in AD in the ADNI. In summary, our integrated analysis of large‐scale multiomics data in AD systematically identifies novel metabolites and their potential regulators in AD and the findings pave a way for not only developing sensitive and specific diagnostic biomarkers for AD but also identifying novel molecular mechanisms of AD pathogenesis.
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    Longitudinal Plasma Metabolomics Profile in Pregnancy—A Study in an Ethnically Diverse U.S. Pregnancy Cohort
    (MDPI, 2021-09-01) Mitro, Susanna D.; Wu, Jing; Rahman, Mohammad L.; Cao, Yaqi; Zhu, Yeyi; Chen, Zhen; Chen, Liwei; Li, Mengying; Hinkle, Stefanie N.; Bremer, Andrew A.; Weir, Natalie L.; Tsai, Michael Y.; Song, Yiqing; Grantz, Katherine L.; Gelaye, Bizu; Zhang, Cuilin; Epidemiology, School of Public Health
    Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n = 214 women at 10-14 and 15-26 weeks, 107 at 26-31 weeks, and 103 at 33-39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.