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

Abstract

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.

QComics: Recommendations and Guidelines for Robust, Easily Implementable and Reportable Quality Control of Metabolomics Data

“…Although it was initially designed for MS-based metabolomics, it should be noted that QC omics can also be used to manage other omics and MS data. In this sense, we would like to stress that some features of this QC protocol have successfully been applied in recent metabolomics and metallomics studies, − which highlights its reliability to deal with complex and heterogeneous data. Therefore, we strongly believe that QC omics will facilitate the implementation of good QC practices, at both application and reporting levels, and thus become a gold standard in metabolomics research.…”

Association between childhood obesity, trace elements, and heavy metals: Recent discoveries and future perspectives

“…In particular, parental obesity was associated with unhealthier outcomes in the offspring (e.g., IR, inflammation and unfavorable lipid profile), in close relationship with exacerbations in the aforementioned metal alterations (i.e., increased copper‐to‐zinc ratios and iron deficiency in circulation, and metal accumulation within erythrocytes). The stratification of the study population according to the insulin secretion profile in response to an oral glucose tolerance test enabled us to demonstrate that participants with late insulin peak, who are characterized by worsened IR and lipid profile, also showed sharpened disturbances in circulating levels of various metals and metalloids 49 . On the one hand, we found children with delayed hyperinsulinemia to have lower plasma contents of chromium and cobalt, which were in turn strongly correlated to various markers of hyperglycemia and dyslipidemia in a negative fashion, probably as a reflection of their vital role in controlling glucose and lipid metabolisms.…”

The mediation effect of Systemic Immunity Inflammation Index between urinary metals and TOFAT among adults in the NHANES dataset

“… 5 – 7 . Previous studies have reported that exposure to As, Cd, cobalt (Co), Pb, and mercury (Hg) could cause chronic diseases such as diabetes and obesity 8 – 10 .…”