PloS one, 2021-12, Vol.16 (12), p.e0261681-e0261681
2021
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- Autor(en) / Beteiligte
- Titel
- A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo
- Ist Teil von
- PloS one, 2021-12, Vol.16 (12), p.e0261681-e0261681
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0261681Titel-ID: cdi_plos_journals_2615611937
- Format
- –
- Schlagworte
- Adipocytes, Adipocytes - metabolism, Adipose tissue, Adipose Tissue - metabolism, Adipose tissues, Adrenergic receptors, Analysis, Biology and Life Sciences, Biomedical engineering, Body fat, Catecholamines, Computer Simulation, Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism, Diabetes, Diabetes mellitus, Diabetes mellitus (non-insulin dependent), Diabetes Mellitus, Type 2 - blood, Engineering, Epinephrine, Experiments, Fatty acids, Fatty Acids - blood, Fatty Acids - metabolism, Glycerol, Health aspects, Humans, In Vitro Techniques, Insulin, Insulin - metabolism, Insulin Resistance, Intracellular, Kinases, Lipolysis, Lipolysis - physiology, Mathematical analysis, Mathematical models, Meals, Medicine and Health Sciences, Modelling, Models, Statistical, Models, Theoretical, Noradrenaline, Norepinephrine, Ordinary differential equations, Organs, Phosphorylation, Physical Sciences, Proteins, Proto-Oncogene Proteins c-akt - metabolism, Receptors, Adrenergic, alpha-2 - metabolism, Receptors, Adrenergic, beta - metabolism, Research and Analysis Methods, Signal Transduction, Software, Systems Biology, Tissue analysis, Triglycerides - metabolism, Uncertainty