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Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity

Insulin resistance in adolescents with obesity associates with a sex‐dependent metabolic ‘signature’ comprising branched‐chain amino acids (BCAAs), glutamate and C3/C5 acylcarnitines (C3/C5), implicating altered flux through BCAA catabolic pathways. Here, we investigated the effects of lifestyle int...

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Autores principales: Jachthuber Trub, Catherine, Balikcioglu, Metin, Freemark, Michael, Bain, James, Muehlbauer, Michael, Ilkayeva, Olga, White, Phillip J., Armstrong, Sarah, Østbye, Truls, Grambow, Steven, Gumus Balikcioglu, Pinar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279626/
https://www.ncbi.nlm.nih.gov/pubmed/34277974
http://dx.doi.org/10.1002/edm2.250
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author Jachthuber Trub, Catherine
Balikcioglu, Metin
Freemark, Michael
Bain, James
Muehlbauer, Michael
Ilkayeva, Olga
White, Phillip J.
Armstrong, Sarah
Østbye, Truls
Grambow, Steven
Gumus Balikcioglu, Pinar
author_facet Jachthuber Trub, Catherine
Balikcioglu, Metin
Freemark, Michael
Bain, James
Muehlbauer, Michael
Ilkayeva, Olga
White, Phillip J.
Armstrong, Sarah
Østbye, Truls
Grambow, Steven
Gumus Balikcioglu, Pinar
author_sort Jachthuber Trub, Catherine
collection PubMed
description Insulin resistance in adolescents with obesity associates with a sex‐dependent metabolic ‘signature’ comprising branched‐chain amino acids (BCAAs), glutamate and C3/C5 acylcarnitines (C3/C5), implicating altered flux through BCAA catabolic pathways. Here, we investigated the effects of lifestyle intervention on BCAA catabolism and insulin sensitivity. We hypothesized (1) weight reduction and improved insulin sensitivity associate with enhanced BCAA catabolism; (2) baseline BCAAs and their metabolic by‐products predict changes in weight and insulin sensitivity during lifestyle intervention. METHODS: A 33 adolescents with obesity were studied before and after 6 months of lifestyle intervention. Principal component analysis and multiple linear regression models were used to correlate changes in metabolic factors with changes in weight and insulin sensitivity assessed by HOMA‐IR, adiponectin and ratio of triglyceride (TG) to HDL. Baseline metabolic factors were used as explanatory variables in prediction models. RESULTS: Weight reduction was associated with reductions in BCAA, glutamate, and C3/C5 (p = .002) and increases in urea cycle AA (p = .029), suggesting an increase in BCAA catabolism. Increases in urea cycle AA during weight reduction were associated with increases in adiponectin, a marker of insulin sensitivity. Markers of insulin resistance (high BCAA, glutamate, and C3/C5 and low urea cycle AA) at baseline predicted increases in metrics of insulin sensitivity (decreased TG/HDL and increased adiponectin) during lifestyle intervention. CONCLUSIONS: Weight reduction in adolescents is associated with increases in BCAA catabolism and improvements in insulin sensitivity. Our study underscores the therapeutic potential of manipulating BCAA catabolism to treat obesity‐associated insulin resistance in adolescents and prevent progression to T2D.
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spelling pubmed-82796262021-07-15 Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity Jachthuber Trub, Catherine Balikcioglu, Metin Freemark, Michael Bain, James Muehlbauer, Michael Ilkayeva, Olga White, Phillip J. Armstrong, Sarah Østbye, Truls Grambow, Steven Gumus Balikcioglu, Pinar Endocrinol Diabetes Metab Original Research Articles Insulin resistance in adolescents with obesity associates with a sex‐dependent metabolic ‘signature’ comprising branched‐chain amino acids (BCAAs), glutamate and C3/C5 acylcarnitines (C3/C5), implicating altered flux through BCAA catabolic pathways. Here, we investigated the effects of lifestyle intervention on BCAA catabolism and insulin sensitivity. We hypothesized (1) weight reduction and improved insulin sensitivity associate with enhanced BCAA catabolism; (2) baseline BCAAs and their metabolic by‐products predict changes in weight and insulin sensitivity during lifestyle intervention. METHODS: A 33 adolescents with obesity were studied before and after 6 months of lifestyle intervention. Principal component analysis and multiple linear regression models were used to correlate changes in metabolic factors with changes in weight and insulin sensitivity assessed by HOMA‐IR, adiponectin and ratio of triglyceride (TG) to HDL. Baseline metabolic factors were used as explanatory variables in prediction models. RESULTS: Weight reduction was associated with reductions in BCAA, glutamate, and C3/C5 (p = .002) and increases in urea cycle AA (p = .029), suggesting an increase in BCAA catabolism. Increases in urea cycle AA during weight reduction were associated with increases in adiponectin, a marker of insulin sensitivity. Markers of insulin resistance (high BCAA, glutamate, and C3/C5 and low urea cycle AA) at baseline predicted increases in metrics of insulin sensitivity (decreased TG/HDL and increased adiponectin) during lifestyle intervention. CONCLUSIONS: Weight reduction in adolescents is associated with increases in BCAA catabolism and improvements in insulin sensitivity. Our study underscores the therapeutic potential of manipulating BCAA catabolism to treat obesity‐associated insulin resistance in adolescents and prevent progression to T2D. John Wiley and Sons Inc. 2021-04-01 /pmc/articles/PMC8279626/ /pubmed/34277974 http://dx.doi.org/10.1002/edm2.250 Text en © 2021 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 Original Research Articles
Jachthuber Trub, Catherine
Balikcioglu, Metin
Freemark, Michael
Bain, James
Muehlbauer, Michael
Ilkayeva, Olga
White, Phillip J.
Armstrong, Sarah
Østbye, Truls
Grambow, Steven
Gumus Balikcioglu, Pinar
Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
title Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
title_full Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
title_fullStr Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
title_full_unstemmed Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
title_short Impact of lifestyle Intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
title_sort impact of lifestyle intervention on branched‐chain amino acid catabolism and insulin sensitivity in adolescents with obesity
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279626/
https://www.ncbi.nlm.nih.gov/pubmed/34277974
http://dx.doi.org/10.1002/edm2.250
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