Please use this identifier to cite or link to this item:
Title: Redox Imbalance and Methylation Disturbances in Early Childhood Obesity
Authors: Barbosa, Pedro 
Melnyk, Stepan
Bennuri, Sirish C
Delhey, Leanna
Reis, Andreia 
Moura, Gabriela R
Børsheim, Elisabet
Rose, Shannon
Carvalho, Eugenia 
Issue Date: 2021
Publisher: Hindawi
Project: National Institute of General Medical Sciences of the National Institutes of Health under a COBRE Award Number P20GM109096 and the Arkansas Biosciences Institute/ Arkansas Children’ Research Institute, through the Discovery Acceleration Initiative/Program Project Planning Grants and bridging funds 
POCI-01-0145-FEDER- 022184 (GenomePT) 
NIH/- NIGMS UL1 TR003107 and KL2 TR003108 and USDA/ARS 6026-51000-012-06-S 
Serial title, monograph or event: Oxidative Medicine and Cellular Longevity
Volume: 2021
Abstract: Obesity is increasing worldwide in prepubertal children, reducing the age of onset of associated comorbidities, including type 2 diabetes. Sulfur-containing amino acids, methionine, cysteine, and their derivatives play important roles in the transmethylation and transsulfuration pathways. Dysregulation of these pathways leads to alterations in the cellular methylation patterns and an imbalanced redox state. Therefore, we tested the hypothesis that one-carbon metabolism is already dysregulated in prepubertal children with obesity. Peripheral blood was collected from 64 children, and the plasma metabolites from transmethylation and transsulfuration pathways were quantified by HPLC. The cohort was stratified by BMI z-scores and HOMA-IR indices into healthy lean (HL), healthy obese (HO), and unhealthy obese (UHO). Fasting insulin levels were higher in the HO group compared to the HL, while the UHO had the highest. All groups presented normal fasting glycemia. Furthermore, high-density lipoprotein (HDL) was lower while triglycerides and lactate levels were higher in the UHO compared to HO subjects. S-adenosylhomocysteine (SAH) and total homocysteine levels were increased in the HO group compared to HL. Additionally, glutathione metabolism was also altered. Free cystine and oxidized glutathione (GSSG) were increased in the HO as compared to HL subjects. Importantly, the adipocyte secretory function was already compromised at this young age. Elevated circulating leptin and decreased adiponectin levels were observed in the UHO as compared to the HO subjects. Some of these alterations were concomitant with alterations in the DNA methylation patterns in the obese group, independent of the impaired insulin levels. In conclusion, our study informs on novel and important metabolic alterations in the transmethylation and the transsulfuration pathways in the early stages of obesity. Moreover, the altered secretory function of the adipocyte very early in life may be relevant in identifying early metabolic markers of disease that may inform on the increased risk for specific future comorbidities in this population.
ISSN: 1942-0994
DOI: 10.1155/2021/2207125
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais

Show full item record


checked on Nov 20, 2023


checked on Nov 2, 2023

Page view(s)

checked on Nov 28, 2023


checked on Nov 28, 2023

Google ScholarTM




This item is licensed under a Creative Commons License Creative Commons