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

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Systems Biology*; Adipocytes/*metabolism ; Adipose Tissue/*metabolism ; Fatty Acids/*metabolism ; Lipolysis/*physiology; Computer Simulation ; Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism ; Diabetes Mellitus, Type 2/blood ; Fatty Acids/blood ; Humans ; In Vitro Techniques ; Insulin/metabolism ; Insulin Resistance ; Models, Statistical ; Models, Theoretical ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Adrenergic, alpha-2/metabolism ; Receptors, Adrenergic, beta/metabolism ; Signal Transduction ; Software ; Triglycerides/metabolism ; Uncertainty
    • 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.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Fatty Acids)
      0 (Insulin)
      0 (Receptors, Adrenergic, alpha-2)
      0 (Receptors, Adrenergic, beta)
      0 (Triglycerides)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
      EC 3.1.4.17 (PDE3B protein, human)
    • Publication Date:
      Date Created: 20211231 Date Completed: 20220118 Latest Revision: 20240405
    • Publication Date:
      20240405
    • Accession Number:
      PMC8719686
    • Accession Number:
      10.1371/journal.pone.0261681
    • Accession Number:
      34972146