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A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo

Lipolysis and the release of fatty acids to supply energy fuel to other organs, such as between meals, during exercise, and starvation, are fundamental functions of the adipose tissue. The intracellular lipolytic pathway in adipocytes is activated by adrenaline and noradrenaline, and inhibited by in...

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Autores principales: Lövfors, William, Ekström, Jona, Jönsson, Cecilia, Strålfors, Peter, Cedersund, Gunnar, Nyman, Elin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719686/
https://www.ncbi.nlm.nih.gov/pubmed/34972146
http://dx.doi.org/10.1371/journal.pone.0261681
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author Lövfors, William
Ekström, Jona
Jönsson, Cecilia
Strålfors, Peter
Cedersund, Gunnar
Nyman, Elin
author_facet Lövfors, William
Ekström, Jona
Jönsson, Cecilia
Strålfors, Peter
Cedersund, Gunnar
Nyman, Elin
author_sort Lövfors, William
collection PubMed
description Lipolysis and the release of fatty acids to supply energy fuel to other organs, such as between meals, during exercise, and starvation, are fundamental functions of the adipose tissue. The intracellular lipolytic pathway in adipocytes is activated by adrenaline and noradrenaline, and inhibited by insulin. Circulating fatty acids are elevated in type 2 diabetic individuals. The mechanisms behind this elevation are not fully known, and to increase the knowledge a link between the systemic circulation and intracellular lipolysis is key. However, data on lipolysis and knowledge from in vitro systems have not been linked to corresponding in vivo data and knowledge in vivo. Here, we use mathematical modelling to provide such a link. We examine mechanisms of insulin action by combining in vivo and in vitro data into an integrated mathematical model that can explain all data. Furthermore, the model can describe independent data not used for training the model. We show the usefulness of the model by simulating new and more challenging experimental setups in silico, e.g. the extracellular concentration of fatty acids during an insulin clamp, and the difference in such simulations between individuals with and without type 2 diabetes. Our work provides a new platform for model-based analysis of adipose tissue lipolysis, under both non-diabetic and type 2 diabetic conditions.
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spelling pubmed-87196862022-01-01 A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo Lövfors, William Ekström, Jona Jönsson, Cecilia Strålfors, Peter Cedersund, Gunnar Nyman, Elin PLoS One Research Article Lipolysis and the release of fatty acids to supply energy fuel to other organs, such as between meals, during exercise, and starvation, are fundamental functions of the adipose tissue. The intracellular lipolytic pathway in adipocytes is activated by adrenaline and noradrenaline, and inhibited by insulin. Circulating fatty acids are elevated in type 2 diabetic individuals. The mechanisms behind this elevation are not fully known, and to increase the knowledge a link between the systemic circulation and intracellular lipolysis is key. However, data on lipolysis and knowledge from in vitro systems have not been linked to corresponding in vivo data and knowledge in vivo. Here, we use mathematical modelling to provide such a link. We examine mechanisms of insulin action by combining in vivo and in vitro data into an integrated mathematical model that can explain all data. Furthermore, the model can describe independent data not used for training the model. We show the usefulness of the model by simulating new and more challenging experimental setups in silico, e.g. the extracellular concentration of fatty acids during an insulin clamp, and the difference in such simulations between individuals with and without type 2 diabetes. Our work provides a new platform for model-based analysis of adipose tissue lipolysis, under both non-diabetic and type 2 diabetic conditions. Public Library of Science 2021-12-31 /pmc/articles/PMC8719686/ /pubmed/34972146 http://dx.doi.org/10.1371/journal.pone.0261681 Text en © 2021 Lövfors et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lövfors, William
Ekström, Jona
Jönsson, Cecilia
Strålfors, Peter
Cedersund, Gunnar
Nyman, Elin
A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
title A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
title_full A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
title_fullStr A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
title_full_unstemmed A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
title_short A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
title_sort systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719686/
https://www.ncbi.nlm.nih.gov/pubmed/34972146
http://dx.doi.org/10.1371/journal.pone.0261681
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