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Fatty acid-induced stress signalling in adipocytes

Brochard, Léa; (2019) Fatty acid-induced stress signalling in adipocytes. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Insulin resistance has been shown to be caused by saturated fatty acids (SFA), especially palmitate found in abundance in the Western diet. The enzyme phosphatidylinositol 3 kinase (PI3K) has been identified as a key modulator of SFAinduced insulin resistance. To further the current understanding of the molecular mechanisms at play, we performed a transcriptome analysis comparing the gene expression profiles of 3T3-L1 adipocytes treated with palmitate, in the presence or absence of an inhibitor selective for p110α, one of the catalytic subunits of class IA PI3K. It revealed that the expression of a number of genes induced by type I interferon (IFN) is stimulated in response to palmitate, an effect abrogated by p110α inhibition. Such finding was of particular interest as IFN is known, like palmitate, to trigger insulin resistance. We studied the molecular links between IFN- and palmitate-mediated insulin resistance in both murine and human pre- and mature adipocytes. This allowed the confirmation of the positive metabolic effect of inhibiting p110α. The effect of palmitate on components of the IFN pathway was further explored and led to the establishment of a pivotal role of IFN-stimulated genes (ISGs) in the development of SFA-induced metabolic dysfunctions in adipocytes.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Fatty acid-induced stress signalling in adipocytes
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10072331
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