{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T20:42:44Z","timestamp":1772829764148,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01899"],"award-info":[{"award-number":["PI22\/01899"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP21\/00120"],"award-info":[{"award-number":["CP21\/00120"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["LII19\/16IN-CO24"],"award-info":[{"award-number":["LII19\/16IN-CO24"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019160","name":"Biomedical Research and Innovation Institute of C\u00e1diz","doi-asserted-by":"publisher","award":["PI22\/01899"],"award-info":[{"award-number":["PI22\/01899"]}],"id":[{"id":"10.13039\/501100019160","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019160","name":"Biomedical Research and Innovation Institute of C\u00e1diz","doi-asserted-by":"publisher","award":["CP21\/00120"],"award-info":[{"award-number":["CP21\/00120"]}],"id":[{"id":"10.13039\/501100019160","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019160","name":"Biomedical Research and Innovation Institute of C\u00e1diz","doi-asserted-by":"publisher","award":["LII19\/16IN-CO24"],"award-info":[{"award-number":["LII19\/16IN-CO24"]}],"id":[{"id":"10.13039\/501100019160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u00b1 2.4 years), middle (N = 16, 11.8 \u00b1 1.9 years), and late (N = 33, 11.7 \u00b1 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 \u00b5g\/L), cobalt (0.79 vs. 1.2 \u00b5g\/L), lead (0.021 vs. 0.025 \u00b5g\/L), and arsenic (0.077 vs. 0.17 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/nu15102347","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T06:32:58Z","timestamp":1684391578000},"page":"2347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-4245","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Gonz\u00e1lez-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Mill\u00e1n-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Associate Unit CSIC-University of Huelva \u201cAtmospheric Pollution\u201d, Center for Research in Sustainable Chemistry-CIQSO, University of Huelva, 21071 Huelva, Spain"},{"name":"Department of Chemistry, Faculty of Experimental Sciences, University of Huelva, 21071 Huelva, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-7940","authenticated-orcid":false,"given":"Jes\u00fas","family":"Dom\u00ednguez-Riscart","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de C\u00e1diz, 11009 C\u00e1diz, Spain"},{"name":"Unidad de Endocrinolog\u00eda Pedi\u00e1trica y Diabetes, Servicio de Pediatr\u00eda, Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-6041","authenticated-orcid":false,"given":"Alfonso Mar\u00eda","family":"Lechuga-Sancho","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de C\u00e1diz, 11009 C\u00e1diz, Spain"},{"name":"Unidad de Endocrinolog\u00eda Pedi\u00e1trica y Diabetes, Servicio de Pediatr\u00eda, Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"},{"name":"Departamento Materno Infantil y Radiolog\u00eda, Facultad de Medicina, Universidad de C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-8833","authenticated-orcid":false,"given":"Ra\u00fal","family":"Gonz\u00e1lez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s10020-021-00394-0","article-title":"Paediatric obesity: A systematic review and pathway mapping of metabolic alterations underlying early disease processes","volume":"27","author":"Gies","year":"2021","journal-title":"Mol. 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