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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/59/10/1785
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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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