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Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.

ABSTRACT: To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations.

SUBMITTER: Troisi J

PROVIDER: S-EPMC5452215 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.

Troisi Jacopo J Pierri Luca L Landolfi Annamaria A Marciano Francesca F Bisogno Antonella A Belmonte Federica F Palladino Carmen C Guercio Nuzio Salvatore S Campiglia Pietro P Vajro Pietro P

Nutrients 20170511 5

To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass ...[more]

PMID: 28492501

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Project description:Naja atra bite is one of the most common severe snakebites in emergency departments. Unfortunately, the pathophysiological changes caused by Naja atra bite are unclear due to the lack of good animal models. In this study, an animal model of Naja atra bite in Guangxi Bama miniature pigs was established by intramuscular injection at 2 mg/kg of Naja atra venom, and serum metabolites were systematically analyzed using untargeted metabolomic and targeted metabolomic approaches. Untargeted metabolomic analysis revealed that 5045 chromatographic peaks were obtained in ESI+ and 3871 chromatographic peaks were obtained in ESI-. Screening in ESI+ modes and ESI- modes identified 22 and 36 differential metabolites compared to controls. The presence of 8 core metabolites of glutamine, arginine, proline, leucine, phenylalanine, inosine, thymidine and hippuric acid in the process of Naja atra bite was verified by targeted metabolomics significant difference (P<0.05). At the same time, during the verification process of the serum clinical samples with Naja atra bite, we found that the contents of three metabolites of proline, phenylalanine and inosine in the serum of the patients were significantly different from those of the normal human serum (P<0.05). By conducting functional analysis of core and metabolic pathway analysis, we revealed a potential correlation between changes in key metabolites after the Naja atra bite and the resulting pathophysiological alterations, and our research aims to establish a theoretical foundation for the prompt diagnosis and treatment of Naja atra bite. Author summary Naja atra bite is one of the most serious tropical and subtropical diseases, and the pathophysiological mechanism of injury caused by Naja atra bite is still not clear, meanwhile, large animal models of Naja atra bite are rarely reported. In this study, a Naja atra bite Bama miniature pig model was constructed and evaluated. In addition, 22 and 36 metabolites were found to be significantly altered in ESI+ and ESI- mode by untargeted metabolomics assay, respectively. More interestingly, 8 of them co-occurred in both ESI+ and ESI- modes. We quantified these 8 metabolites absolutely by targeted metabolomics and validated them in the serum of Naja atra bite patients, which showed the same trend as the untargeted metabolomics results. We also compared the differences in the levels of these 8 metabolites in the serum of the Naja atra bite patient group and the normal human group, we found decreased expression of inosine, proline and phenylalanine. Based on this, we compared the blood metabolic profiles with those of Bungarus multicinctus and Trimeresurus stejnegeri, and finally we confirmed that inosine, proline and phenylalanine are likely to be the key metabolites in Naja atra bite.

Dataset Information

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.

Publications

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.

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