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Metabolites
Special Issues
Determinants, Mechanisms, and Consequences of Childhood Obesity
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Determinants, Mechanisms, and Consequences of Childhood Obesity

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 11063

Special Issue Editors

Dr. Wei Perng

E-Mail Website
Guest Editor
Department of Epidemiology, Colorado School of Public Health, Lifecourse Epidemiology of Adiposity & Diabetes Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Interests: metabolomics; childhood obesity; youth-onset type 2 diabetes; nutrition; lifecourse epidemiology; causal inference
Dr. Catherine C. Cohen

E-Mail Website
Guest Editor
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Interests: nutrition science; childhood obesity; pediatric nonalcoholic fatty liver disease; omics; lifecourse research; dietary assessment
Dr. Ellen C. Francis

E-Mail Website
Guest Editor
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Interests: fetal overnutrition; pediatric insulin resistance; precision medicine; metabolomics; developmental origins of health and disease

Special Issue Information

Dear Colleagues,

Metabolomics is the comprehensive and systematic study of low-molecular-weight compounds in biological tissues and fluids. As the most downstream component of the ‘omics cascade, metabolomics reflects an integration of “above-the-skin” exposures and risk factors, as well as intrinsic physiology owing to upstream ‘omics (genetics, epigenomics, transcriptomics, and proteomics). These unique characteristics make metabolomics profiling a powerful tool for identifying novel biomarkers of difficult-to-measure exposures, characterize pathophysiologic mechanisms, and refine assessment of preclinical or clinical disease phenotypes. In recent years, the application of metabolite profiling to epidemiological studies has become possible due to technological advancements in the field, allowing for large-scale population-based investigations of chronic disease risk assessment and prognosis. This Special Issue highlights the use of metabolomics in epidemiological research on determinants, mechanisms, and consequences of childhood obesity. Specific areas include, but not limited to, use of metabolomics to identify novel biomarkers of childhood obesity and related metabolic sequelae (e.g., non-alcoholic fatty liver disease, metabolic syndrome, type 2 diabetes, as well as markers of preclinical progression of these diseases), biomarkers of established risk factors of childhood obesity (e.g., obesogenic in utero exposures, dietary intake, activity level, environmental exposures), and identification of mechanistic pathways linking risk factors and exposures to obesity-related outcomes in youth.

Dr. Wei Perng
Dr. Catherine C. Cohen
Dr. Ellen C. Francis
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolomics
  • metabolites
  • childhood obesity
  • childhood metabolic risk
  • dietary intake
  • epidemiology
  • metabolism

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Published Papers (4 papers)

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Research

12 pages, 324 KiB  
Article
Epigenetic Age Acceleration in Mothers and Offspring 4–10 Years after a Pregnancy Complicated by Gestational Diabetes and Obesity
by Nita Kanney, Amit Patki, Paula Chandler-Laney, W. Timothy Garvey and Bertha A. Hidalgo
Metabolites 2022, 12(12), 1226; https://doi.org/10.3390/metabo12121226 - 7 Dec 2022
Cited by 8 | Viewed by 2606
Abstract
A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 [...] Read more.
A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 mother-child dyads with an index pregnancy 4–10 years before study enrollment were included. Clinical data and whole blood samples were collected and quantified to obtain DNA methylation (DNAm) estimates using the Illumina MethylEPIC 850K array in mothers and offspring. DNAm age and age acceleration were evaluated using the Horvath and Hannum clocks. Multivariable linear regression models were performed to determine the association between EAA and leptin, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, and HOMA-IR. Mothers with a GDM and non-GDM pregnancy had strong correlations between chronological age and DNAm age (r > 0.70). Offspring of GDM mothers had moderate to strong correlations, whereas offspring of non-GDM mothers had moderate correlations between chronological age and DNAm age. Association analyses revealed a significant association between EAA and fasting insulin in offspring (FDR < 0.05), while HDL-C was the only metabolic marker significantly associated with EAA in mothers (FDR < 0.05). Mothers in the GDM group had a higher predicted epigenetic age and age acceleration than mothers in the non-GDM group. The association between EAA with elevated fasting insulin in offspring and elevated HDL-C in mothers suggests possible biomarkers that can better elucidate the effects of exposure to a GDM pregnancy and future cardiometabolic outcomes. Full article
(This article belongs to the Special Issue Determinants, Mechanisms, and Consequences of Childhood Obesity)
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16 pages, 829 KiB  
Article
Metabolome Alterations Linking Sugar-Sweetened Beverage Intake with Dyslipidemia in Youth: The Exploring Perinatal Outcomes among CHildren (EPOCH) Study
by Catherine C. Cohen, Dana Dabelea, Gregory Michelotti, Lu Tang, Kartik Shankar, Michael I. Goran and Wei Perng
Metabolites 2022, 12(6), 559; https://doi.org/10.3390/metabo12060559 - 17 Jun 2022
Cited by 2 | Viewed by 2635
Abstract
The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in [...] Read more.
The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in childhood (median 10 yrs) and adolescence (median 16 yrs). We used a multi-step approach: first, mixed models were used to examine the associations of SSB intake in childhood with CM measures across childhood and adolescence, which revealed a positive association between SSB intake and fasting triglycerides (β (95% CI) for the highest vs. lowest SSB quartile: 8.1 (−0.9,17.0); p-trend = 0.057). Second, least absolute shrinkage and selection operator (LASSO) regression was used to select 180 metabolite features (out of 767 features assessed by untargeted metabolomics) that were associated with SSB intake in childhood. Finally, 13 of these SSB-associated metabolites (from step two) were also prospectively associated with triglycerides across follow-up (from step one) in the same direction as with SSB intake (Bonferroni-adj. p < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. In this diverse cohort, we identified a panel of lipid metabolites that may serve as intermediary biomarkers, linking SSB intake to dyslipidemia risk in youth. Full article
(This article belongs to the Special Issue Determinants, Mechanisms, and Consequences of Childhood Obesity)
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Figure 1

11 pages, 256 KiB  
Article
Associations of Cord Blood Lipids with Childhood Adiposity at the Age of Three Years: A Prospective Birth Cohort Study
by Qi-Qing Ye, Shao-Min Kong, Xin Yin, Chang Gao, Min-Shan Lu, Rema Ramakrishnan, Cheng Guo, Wang Yao, Ji-Yuan Zeng, Ya-Shu Kuang, Jin-Hua Lu, Jian-Rong He and Xiu Qiu
Metabolites 2022, 12(6), 522; https://doi.org/10.3390/metabo12060522 - 6 Jun 2022
Cited by 5 | Viewed by 2403
Abstract
We aimed to examine the associations between cord blood lipids and childhood adiposity and to investigate whether these associations vary across birth weight categories (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) in 1306 infants [...] Read more.
We aimed to examine the associations between cord blood lipids and childhood adiposity and to investigate whether these associations vary across birth weight categories (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) in 1306 infants in the Born in Guangzhou Cohort Study, China. Adiposity outcomes at the age of three years included z-scores of weight-for-length/height (WFLZ), body mass index (BMIZ), subscapular (SSTZ) and triceps skinfold thickness (TSTZ), and the sum of skinfold thicknesses (SSFTZ). Cord blood triglycerides (TG) levels were negatively associated with WFLZ and BMIZ, whereas high density lipoprotein (HDL) levels were positively associated with WFLZ, BMIZ, TSTZ and SSFTZ. These associations were attenuated after adjustment for birth weight. Stratified analyses revealed that total cholesterol (TC) and low-density lipoprotein (LDL) levels were positively associated with childhood adiposity indicators among AGA infants but tended to be negatively associated with the adiposity indicators among LGA infants (p values for interaction <0.05). Furthermore, TG levels appeared to be positively associated with adiposity indicators among SGA infants but negatively associated with the outcomes among LGA infants (p values for interaction <0.05). Cord blood lipids levels might be associated with childhood adiposity, and these associations appear to differ across different birth weight categories. If confirmed in future studies, our findings suggest that individualized management plans might be warranted in preventing obesity. Full article
(This article belongs to the Special Issue Determinants, Mechanisms, and Consequences of Childhood Obesity)
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13 pages, 297 KiB  
Article
Metabolomic Predictors of Dysglycemia in Two U.S. Youth Cohorts
by Wei Perng, Marie-France Hivert, Gregory Michelotti, Emily Oken and Dana Dabelea
Metabolites 2022, 12(5), 404; https://doi.org/10.3390/metabo12050404 - 29 Apr 2022
Cited by 2 | Viewed by 1769
Abstract
Here, we seek to identify metabolite predictors of dysglycemia in youth. In the discovery analysis among 391 youth in the Exploring Perinatal Outcomes among CHildren (EPOCH) cohort, we used reduced rank regression (RRR) to identify sex-specific metabolite predictors of impaired fasting glucose (IFG) [...] Read more.
Here, we seek to identify metabolite predictors of dysglycemia in youth. In the discovery analysis among 391 youth in the Exploring Perinatal Outcomes among CHildren (EPOCH) cohort, we used reduced rank regression (RRR) to identify sex-specific metabolite predictors of impaired fasting glucose (IFG) and elevated fasting glucose (EFG: Q4 vs. Q1 fasting glucose) 6 years later and compared the predictive capacity of four models: Model 1: ethnicity, parental diabetes, in utero exposure to diabetes, and body mass index (BMI); Model 2: Model 1 covariates + baseline waist circumference, insulin, lipids, and Tanner stage; Model 3: Model 2 + baseline fasting glucose; Model 4: Model 3 + baseline metabolite concentrations. RRR identified 19 metabolite predictors of fasting glucose in boys and 14 metabolite predictors in girls. Most compounds were on lipid, amino acid, and carbohydrate metabolism pathways. In boys, no improvement in aurea under the receiver operating characteristics curve AUC occurred until the inclusion of metabolites in Model 4, which increased the AUC for prediction of IFG (7.1%) from 0.81 to 0.97 (p = 0.002). In girls, %IFG was too low for regression analysis (3.1%), but we found similar results for EFG. We replicated the results among 265 youth in the Project Viva cohort, focusing on EFG due to low %IFG, suggesting that the metabolite profiles identified herein have the potential to improve the prediction of glycemia in youth. Full article
(This article belongs to the Special Issue Determinants, Mechanisms, and Consequences of Childhood Obesity)
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