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

Lövfors, William and Ekström, Jona and Jönsson, Cecilia and Strålfors, Peter and Cedersund, Gunnar and Nyman, Elin and Oberer, Monika (2021) A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo. PLOS ONE, 16 (12). e0261681. ISSN 1932-6203

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Abstract

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.

Item Type: Article
Subjects: EP Archives > Medical Science
Depositing User: Managing Editor
Date Deposited: 15 Mar 2023 09:41
Last Modified: 03 Jan 2024 06:31
URI: http://research.send4journal.com/id/eprint/689

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