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Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart
Background: Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity. Despite studies supporting the linkages of increased systemic branched-chain amino acids (BCAAs) d...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438793/ https://www.ncbi.nlm.nih.gov/pubmed/32903728 http://dx.doi.org/10.3389/fendo.2020.00534 |
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author | Biswas, Dipsikha Tozer, Kathleen Dao, Khoi T. Perez, Lester J. Mercer, Angella Brown, Amy Hossain, Intekhab Yip, Alexandra M. Aguiar, Christie Motawea, Hany Brunt, Keith R. Shea, Jennifer Legare, Jean F. Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas |
author_facet | Biswas, Dipsikha Tozer, Kathleen Dao, Khoi T. Perez, Lester J. Mercer, Angella Brown, Amy Hossain, Intekhab Yip, Alexandra M. Aguiar, Christie Motawea, Hany Brunt, Keith R. Shea, Jennifer Legare, Jean F. Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas |
author_sort | Biswas, Dipsikha |
collection | PubMed |
description | Background: Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity. Despite studies supporting the linkages of increased systemic branched-chain amino acids (BCAAs) driving the pathogenesis of obesity, metabolome wide studies have either supported or challenged association of circulating BCAAs with cardiovascular diseases (CVDs). Objective: We interrogated whether BCAA catabolic changes precipitated by obesity in the heart and adipose tissue can be reliable prognosticators of adverse outcomes following cardiac surgery. Our study specifically clarified the correlation between BCAA catabolizing enzymes, cellular BCAAs and branched-chain keto acids (BCKAs) with the severity of cardiometabolic outcomes in obese patients pre and post cardiac surgery. Methods: Male and female patients of ages between 44 and 75 were stratified across different body mass index (BMI) (non-obese = 17, pre-obese = 19, obese class I = 14, class II = 17, class III = 12) and blood, atrial appendage (AA), and subcutaneous adipose tissue (SAT) collected during cardiac surgery. Plasma and intracellular BCAAs and BC ketoacids (BCKAs), tissue mRNA and protein expression and activity of BCAA catabolizing enzymes were assessed and correlated with clinical parameters. Results: Intramyocellular, but not systemic, BCAAs increased with BMI in cardiac surgery patients. In SAT, from class III obese patients, mRNA and protein expression of BCAA catabolic enzymes and BCKA dehydrogenase (BCKDH) enzyme activity was decreased. Within AA, a concomitant increase in mRNA levels of BCAA metabolizing enzymes was observed, independent of changes in BCKDH protein expression or activity. BMI, indices of tissue dysfunction and duration of hospital stay following surgery correlated with BCAA metabolizing enzyme expression and metabolite levels in AA and SAT. Conclusion: This study proposes that in a setting of obesity, dysregulated BCAA catabolism could be an effective surrogate to determine cardiac surgery outcomes and plausibly predict premature re-hospitalization. |
format | Online Article Text |
id | pubmed-7438793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74387932020-09-03 Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart Biswas, Dipsikha Tozer, Kathleen Dao, Khoi T. Perez, Lester J. Mercer, Angella Brown, Amy Hossain, Intekhab Yip, Alexandra M. Aguiar, Christie Motawea, Hany Brunt, Keith R. Shea, Jennifer Legare, Jean F. Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas Front Endocrinol (Lausanne) Endocrinology Background: Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity. Despite studies supporting the linkages of increased systemic branched-chain amino acids (BCAAs) driving the pathogenesis of obesity, metabolome wide studies have either supported or challenged association of circulating BCAAs with cardiovascular diseases (CVDs). Objective: We interrogated whether BCAA catabolic changes precipitated by obesity in the heart and adipose tissue can be reliable prognosticators of adverse outcomes following cardiac surgery. Our study specifically clarified the correlation between BCAA catabolizing enzymes, cellular BCAAs and branched-chain keto acids (BCKAs) with the severity of cardiometabolic outcomes in obese patients pre and post cardiac surgery. Methods: Male and female patients of ages between 44 and 75 were stratified across different body mass index (BMI) (non-obese = 17, pre-obese = 19, obese class I = 14, class II = 17, class III = 12) and blood, atrial appendage (AA), and subcutaneous adipose tissue (SAT) collected during cardiac surgery. Plasma and intracellular BCAAs and BC ketoacids (BCKAs), tissue mRNA and protein expression and activity of BCAA catabolizing enzymes were assessed and correlated with clinical parameters. Results: Intramyocellular, but not systemic, BCAAs increased with BMI in cardiac surgery patients. In SAT, from class III obese patients, mRNA and protein expression of BCAA catabolic enzymes and BCKA dehydrogenase (BCKDH) enzyme activity was decreased. Within AA, a concomitant increase in mRNA levels of BCAA metabolizing enzymes was observed, independent of changes in BCKDH protein expression or activity. BMI, indices of tissue dysfunction and duration of hospital stay following surgery correlated with BCAA metabolizing enzyme expression and metabolite levels in AA and SAT. Conclusion: This study proposes that in a setting of obesity, dysregulated BCAA catabolism could be an effective surrogate to determine cardiac surgery outcomes and plausibly predict premature re-hospitalization. Frontiers Media S.A. 2020-08-07 /pmc/articles/PMC7438793/ /pubmed/32903728 http://dx.doi.org/10.3389/fendo.2020.00534 Text en Copyright © 2020 Biswas, Tozer, Dao, Perez, Mercer, Brown, Hossain, Yip, Aguiar, Motawea, Brunt, Shea, Legare, Hassan, Kienesberger and Pulinilkunnil. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Biswas, Dipsikha Tozer, Kathleen Dao, Khoi T. Perez, Lester J. Mercer, Angella Brown, Amy Hossain, Intekhab Yip, Alexandra M. Aguiar, Christie Motawea, Hany Brunt, Keith R. Shea, Jennifer Legare, Jean F. Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart |
title | Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart |
title_full | Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart |
title_fullStr | Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart |
title_full_unstemmed | Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart |
title_short | Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart |
title_sort | adverse outcomes in obese cardiac surgery patients correlates with altered branched-chain amino acid catabolism in adipose tissue and heart |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438793/ https://www.ncbi.nlm.nih.gov/pubmed/32903728 http://dx.doi.org/10.3389/fendo.2020.00534 |
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