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Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity

Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of pl...

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Autores principales: González-Domínguez, Álvaro, Millán-Martínez, María, Domínguez-Riscart, Jesús, Lechuga-Sancho, Alfonso María, González-Domínguez, Raúl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221169/
https://www.ncbi.nlm.nih.gov/pubmed/37242230
http://dx.doi.org/10.3390/nu15102347
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author González-Domínguez, Álvaro
Millán-Martínez, María
Domínguez-Riscart, Jesús
Lechuga-Sancho, Alfonso María
González-Domínguez, Raúl
author_facet González-Domínguez, Álvaro
Millán-Martínez, María
Domínguez-Riscart, Jesús
Lechuga-Sancho, Alfonso María
González-Domínguez, Raúl
author_sort González-Domínguez, Álvaro
collection PubMed
description Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. Results: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity.
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spelling pubmed-102211692023-05-28 Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity González-Domínguez, Álvaro Millán-Martínez, María Domínguez-Riscart, Jesús Lechuga-Sancho, Alfonso María González-Domínguez, Raúl Nutrients Article Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. Results: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity. MDPI 2023-05-17 /pmc/articles/PMC10221169/ /pubmed/37242230 http://dx.doi.org/10.3390/nu15102347 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
González-Domínguez, Álvaro
Millán-Martínez, María
Domínguez-Riscart, Jesús
Lechuga-Sancho, Alfonso María
González-Domínguez, Raúl
Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
title Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
title_full Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
title_fullStr Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
title_full_unstemmed Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
title_short Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
title_sort metal homeostasis and exposure in distinct phenotypic subtypes of insulin resistance among children with obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221169/
https://www.ncbi.nlm.nih.gov/pubmed/37242230
http://dx.doi.org/10.3390/nu15102347
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