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OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?

Disclosure: M. Calvert: None. S. Molsberry: None. A.K. Jarmusch: None. K.E. Overdahl: None. N. Shaw: None. Introduction: The Body Weight and Puberty Study (BWPS) was a 4-year longitudinal study of 90 healthy pubertal, pre-menarchal girls consisting of dual-energy x-ray absorptiometry to calculate to...

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Autores principales: Calvert, Madison, Molsberry, Samantha, Jarmusch, Alan K, Overdahl, Kirsten E, Shaw, Natalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10555430/
http://dx.doi.org/10.1210/jendso/bvad114.1509
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author Calvert, Madison
Molsberry, Samantha
Jarmusch, Alan K
Overdahl, Kirsten E
Shaw, Natalie
author_facet Calvert, Madison
Molsberry, Samantha
Jarmusch, Alan K
Overdahl, Kirsten E
Shaw, Natalie
author_sort Calvert, Madison
collection PubMed
description Disclosure: M. Calvert: None. S. Molsberry: None. A.K. Jarmusch: None. K.E. Overdahl: None. N. Shaw: None. Introduction: The Body Weight and Puberty Study (BWPS) was a 4-year longitudinal study of 90 healthy pubertal, pre-menarchal girls consisting of dual-energy x-ray absorptiometry to calculate total body fat (TBF), Tanner staging, breast ultrasound, and hormone tests. We observed that with time, girls with higher TBF demonstrated higher serum total and free testosterone and androstenedione levels. The cause of this association is unknown but is hypothesized to relate to greater insulin resistance. Methods: To investigate the association between higher androgens and higher TBF in late pubertal girls, we conducted an untargeted metabolomics study using our BWPS collection of 158 blood and 178 urine samples. Samples were run on an ultra-high performance liquid chromatograph (Vanquish, Thermo Scientific) coupled to a high-resolution mass spectrometer (Orbitrap Fusion Tribrid, Thermo Scientific) and analyzed in positive and negative ionization modes. We investigated the association between TBF or BMI Z-score and metabolites and the association between metabolites and serum androgen levels. All associations were examined cross-sectionally and lagged by one visit using linear generalized estimating equation models, adjusting for breast morphological stage and age at baseline, race, and time between visits. Benjamini-Hochberg false discovery rate (FDR) adjusted p-values were calculated to account for multiple testing. RaMP DB (Relational database of Metabolomic Pathways) was used to conduct enriched pathway analyses among metabolites nominally associated with body composition or hormone levels. Results: 70 participants (aged 10.9 ± 1.39 SD years; 60% White, 24% Black, 16% Other; 63% normal weight, 37% overweight/obese) contributed an average of 2.39 blood and 2.54 urine samples over the course of 1.15 ± 0.47 SD years of follow-up. While few metabolites were significantly associated with body composition or androgen levels after strict multiple testing correction, RaMP DB enriched pathway analyses identified several pathways linking TBF and androgen levels: 1) in lagged analyses of urinary metabolites, overall amino acid metabolism, arginine and proline metabolism, and the urea cycle linked TBF with androstenedione; 2) in cross-sectional analyses of serum metabolites, bile acid synthesis and metabolism, VEGF or extra-nuclear estrogen signaling (related to the metabolite, sphingosine-1-phosphate), and tryptophan metabolism linked TBF with androstenedione. Conclusions: Metabolomic analyses of samples from pubertal girls did not uncover signatures of insulin resistance (e.g., branched chain amino acids or C3- and C5-acyclcarnitines) to explain the association between higher androgens and TBF. Instead, we identified potential novel signaling pathways that may involve amino acid, bile acid, or sphingosine-1-phosphate action at the ovary and/or adrenal gland. Presentation: Friday, June 16, 2023
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spelling pubmed-105554302023-10-06 OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why? Calvert, Madison Molsberry, Samantha Jarmusch, Alan K Overdahl, Kirsten E Shaw, Natalie J Endocr Soc Pediatric Endocrinology Disclosure: M. Calvert: None. S. Molsberry: None. A.K. Jarmusch: None. K.E. Overdahl: None. N. Shaw: None. Introduction: The Body Weight and Puberty Study (BWPS) was a 4-year longitudinal study of 90 healthy pubertal, pre-menarchal girls consisting of dual-energy x-ray absorptiometry to calculate total body fat (TBF), Tanner staging, breast ultrasound, and hormone tests. We observed that with time, girls with higher TBF demonstrated higher serum total and free testosterone and androstenedione levels. The cause of this association is unknown but is hypothesized to relate to greater insulin resistance. Methods: To investigate the association between higher androgens and higher TBF in late pubertal girls, we conducted an untargeted metabolomics study using our BWPS collection of 158 blood and 178 urine samples. Samples were run on an ultra-high performance liquid chromatograph (Vanquish, Thermo Scientific) coupled to a high-resolution mass spectrometer (Orbitrap Fusion Tribrid, Thermo Scientific) and analyzed in positive and negative ionization modes. We investigated the association between TBF or BMI Z-score and metabolites and the association between metabolites and serum androgen levels. All associations were examined cross-sectionally and lagged by one visit using linear generalized estimating equation models, adjusting for breast morphological stage and age at baseline, race, and time between visits. Benjamini-Hochberg false discovery rate (FDR) adjusted p-values were calculated to account for multiple testing. RaMP DB (Relational database of Metabolomic Pathways) was used to conduct enriched pathway analyses among metabolites nominally associated with body composition or hormone levels. Results: 70 participants (aged 10.9 ± 1.39 SD years; 60% White, 24% Black, 16% Other; 63% normal weight, 37% overweight/obese) contributed an average of 2.39 blood and 2.54 urine samples over the course of 1.15 ± 0.47 SD years of follow-up. While few metabolites were significantly associated with body composition or androgen levels after strict multiple testing correction, RaMP DB enriched pathway analyses identified several pathways linking TBF and androgen levels: 1) in lagged analyses of urinary metabolites, overall amino acid metabolism, arginine and proline metabolism, and the urea cycle linked TBF with androstenedione; 2) in cross-sectional analyses of serum metabolites, bile acid synthesis and metabolism, VEGF or extra-nuclear estrogen signaling (related to the metabolite, sphingosine-1-phosphate), and tryptophan metabolism linked TBF with androstenedione. Conclusions: Metabolomic analyses of samples from pubertal girls did not uncover signatures of insulin resistance (e.g., branched chain amino acids or C3- and C5-acyclcarnitines) to explain the association between higher androgens and TBF. Instead, we identified potential novel signaling pathways that may involve amino acid, bile acid, or sphingosine-1-phosphate action at the ovary and/or adrenal gland. Presentation: Friday, June 16, 2023 Oxford University Press 2023-10-05 /pmc/articles/PMC10555430/ http://dx.doi.org/10.1210/jendso/bvad114.1509 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Pediatric Endocrinology
Calvert, Madison
Molsberry, Samantha
Jarmusch, Alan K
Overdahl, Kirsten E
Shaw, Natalie
OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?
title OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?
title_full OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?
title_fullStr OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?
title_full_unstemmed OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?
title_short OR15-01 Overweight/Obese Pubertal Girls Have Higher Androgen Levels - Can Metabolomics Tell Us Why?
title_sort or15-01 overweight/obese pubertal girls have higher androgen levels - can metabolomics tell us why?
topic Pediatric Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10555430/
http://dx.doi.org/10.1210/jendso/bvad114.1509
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