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Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity

OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex‐dependent metabolic ‘signature’ comprising the branched‐chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched‐chain α‐keto acids (BCKAs) and...

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Autores principales: Gumus Balikcioglu, Pinar, Jachthuber Trub, Catherine, Balikcioglu, Metin, Ilkayeva, Olga, White, Phillip J., Muehlbauer, Michael, Bain, James R., Armstrong, Sarah, Freemark, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836245/
https://www.ncbi.nlm.nih.gov/pubmed/36415168
http://dx.doi.org/10.1002/edm2.388
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author Gumus Balikcioglu, Pinar
Jachthuber Trub, Catherine
Balikcioglu, Metin
Ilkayeva, Olga
White, Phillip J.
Muehlbauer, Michael
Bain, James R.
Armstrong, Sarah
Freemark, Michael
author_facet Gumus Balikcioglu, Pinar
Jachthuber Trub, Catherine
Balikcioglu, Metin
Ilkayeva, Olga
White, Phillip J.
Muehlbauer, Michael
Bain, James R.
Armstrong, Sarah
Freemark, Michael
author_sort Gumus Balikcioglu, Pinar
collection PubMed
description OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex‐dependent metabolic ‘signature’ comprising the branched‐chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched‐chain α‐keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6‐month lifestyle‐intervention program. METHODS: Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12–18 year) were analysed by flow‐injection tandem MS and LC–MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA‐IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables. RESULTS: Baseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI‐metrics. Following lifestyle‐intervention, α‐keto‐β‐methylvalerate (α‐KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA‐IR at 6‐month‐follow‐up. Glutamate/glutamine was positively associated with HOMA‐IR at baseline and 6‐month‐follow‐up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6‐month‐follow‐up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight. CONCLUSIONS: BCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle‐intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis.
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spelling pubmed-98362452023-01-18 Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity Gumus Balikcioglu, Pinar Jachthuber Trub, Catherine Balikcioglu, Metin Ilkayeva, Olga White, Phillip J. Muehlbauer, Michael Bain, James R. Armstrong, Sarah Freemark, Michael Endocrinol Diabetes Metab Research Articles OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex‐dependent metabolic ‘signature’ comprising the branched‐chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched‐chain α‐keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6‐month lifestyle‐intervention program. METHODS: Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12–18 year) were analysed by flow‐injection tandem MS and LC–MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA‐IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables. RESULTS: Baseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI‐metrics. Following lifestyle‐intervention, α‐keto‐β‐methylvalerate (α‐KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA‐IR at 6‐month‐follow‐up. Glutamate/glutamine was positively associated with HOMA‐IR at baseline and 6‐month‐follow‐up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6‐month‐follow‐up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight. CONCLUSIONS: BCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle‐intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis. John Wiley and Sons Inc. 2022-11-22 /pmc/articles/PMC9836245/ /pubmed/36415168 http://dx.doi.org/10.1002/edm2.388 Text en © 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Gumus Balikcioglu, Pinar
Jachthuber Trub, Catherine
Balikcioglu, Metin
Ilkayeva, Olga
White, Phillip J.
Muehlbauer, Michael
Bain, James R.
Armstrong, Sarah
Freemark, Michael
Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity
title Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity
title_full Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity
title_fullStr Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity
title_full_unstemmed Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity
title_short Branched‐chain α‐keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity
title_sort branched‐chain α‐keto acids and glutamate/glutamine: biomarkers of insulin resistance in childhood obesity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836245/
https://www.ncbi.nlm.nih.gov/pubmed/36415168
http://dx.doi.org/10.1002/edm2.388
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