RT Journal Article T1 Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity A1 González Domínguez, Álvaro A1 Millán Martínez, María A1 Domínguez Riscart, Jesús A1 Lechuga Sancho, Alfonso María A1 González Domínguez, Raúl AB 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. PB MDPI SN 2072-6643 (electrónico) YR 2023 FD 2023-05 LK https://hdl.handle.net/10272/22422 UL https://hdl.handle.net/10272/22422 LA eng NO González-Domínguez, Á., Millán-Martínez, M., Domínguez-Riscart, J., Lechuga-Sancho, A. M., & González-Domínguez, R. (2023). Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity. In Nutrients (Vol. 15, Issue 10, p. 2347). MDPI AG. https://doi.org/10.3390/nu15102347 NO This research was funded by the Spanish Government through Instituto de Salud Carlos III (PI22/01899). AGD is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and RGD is a recipient of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III. DS Repositorio Institucional de la Universidad de Huelva RD 31 may 2026