Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity
<i>Background and Objectives</i>: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated wit...
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MDPI AG
2023-10-01
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author | Nayely Garibay-Nieto Karen Pedraza-Escudero Isabel Omaña-Guzmán María José Garcés-Hernández Eréndira Villanueva-Ortega Mariana Flores-Torres José Luis Pérez-Hernández Mireya León-Hernández Estibalitz Laresgoiti-Servitje Berenice Palacios-González Juan Carlos López-Alvarenga Mauricio Lisker-Melman Felipe Vadillo-Ortega |
author_facet | Nayely Garibay-Nieto Karen Pedraza-Escudero Isabel Omaña-Guzmán María José Garcés-Hernández Eréndira Villanueva-Ortega Mariana Flores-Torres José Luis Pérez-Hernández Mireya León-Hernández Estibalitz Laresgoiti-Servitje Berenice Palacios-González Juan Carlos López-Alvarenga Mauricio Lisker-Melman Felipe Vadillo-Ortega |
author_sort | Nayely Garibay-Nieto |
collection | DOAJ |
description | <i>Background and Objectives</i>: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. <i>Materials and Methods</i>: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan<sup>®</sup> Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. <i>Results</i>: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. <i>Conclusions</i>: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents. |
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spelling | doaj.art-d66047cb19fd40e99a24efeaf21378182023-11-19T17:17:11ZengMDPI AGMedicina1010-660X1648-91442023-10-015910178510.3390/medicina59101785Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with ObesityNayely Garibay-Nieto0Karen Pedraza-Escudero1Isabel Omaña-Guzmán2María José Garcés-Hernández3Eréndira Villanueva-Ortega4Mariana Flores-Torres5José Luis Pérez-Hernández6Mireya León-Hernández7Estibalitz Laresgoiti-Servitje8Berenice Palacios-González9Juan Carlos López-Alvarenga10Mauricio Lisker-Melman11Felipe Vadillo-Ortega12Pediatric Obesity Clinic and Wellness Unit, General Hospital of Mexico, Mexico City 06720, MexicoPediatric Obesity Clinic and Wellness Unit, General Hospital of Mexico, Mexico City 06720, MexicoPediatric Obesity Clinic and Wellness Unit, General Hospital of Mexico, Mexico City 06720, MexicoPediatric Obesity Clinic and Wellness Unit, General Hospital of Mexico, Mexico City 06720, MexicoPediatric Obesity Clinic and Wellness Unit, General Hospital of Mexico, Mexico City 06720, MexicoUnidad de Vinculación de la Facultad de Medicina, UNAM, Instituto Nacional de Medicina Genómica, Mexico City 14610, MexicoHepatology Clinic, Gastroenterology Department, General Hospital of Mexico, Mexico City 06720, MexicoResearch Unit, General Hospital of Mexico, Mexico City 06720, MexicoClinical Health Sciences, School of Medicine and Health Sciences, Tecnológico de Monterrey, Monterrey 64849, MexicoLaboratorio de Envejecimiento Saludable, Centro de Investigación Sobre el Envejecimiento, Instituto Nacional de Medicina Genómica, Mexico City 14610, MexicoDepartment of Population Health & Biostatistics, University of Texas Rio Grande Valley, Edinburg, TX 78539, USADivision of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110, USAUnidad de Vinculación de la Facultad de Medicina, UNAM, Instituto Nacional de Medicina Genómica, Mexico City 14610, Mexico<i>Background and Objectives</i>: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. <i>Materials and Methods</i>: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan<sup>®</sup> Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. <i>Results</i>: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. <i>Conclusions</i>: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.https://www.mdpi.com/1648-9144/59/10/1785MASLDmetabolomicschildrenobesityamino acidsacylcarnitine |
spellingShingle | Nayely Garibay-Nieto Karen Pedraza-Escudero Isabel Omaña-Guzmán María José Garcés-Hernández Eréndira Villanueva-Ortega Mariana Flores-Torres José Luis Pérez-Hernández Mireya León-Hernández Estibalitz Laresgoiti-Servitje Berenice Palacios-González Juan Carlos López-Alvarenga Mauricio Lisker-Melman Felipe Vadillo-Ortega Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity Medicina MASLD metabolomics children obesity amino acids acylcarnitine |
title | Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity |
title_full | Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity |
title_fullStr | Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity |
title_full_unstemmed | Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity |
title_short | Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity |
title_sort | metabolomic phenotype of hepatic steatosis and fibrosis in mexican children living with obesity |
topic | MASLD metabolomics children obesity amino acids acylcarnitine |
url | https://www.mdpi.com/1648-9144/59/10/1785 |
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