NDLI: Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays

Content Provider	Springer Nature : BioMed Central
Author	González-Domínguez, Álvaro Savolainen, Otto Domínguez-Riscart, Jesús Landberg, Rikard Lechuga-Sancho, Alfonso González-Domínguez, Raúl
Abstract	Background Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. Methods To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Results Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Conclusions Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-024-02395-9.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-024-02395-9
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2024-09-11
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology Childhood obesity Erythrocytes Insulin resistance Metabolomics
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

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