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    iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy


    Lynch, Lydia and Hogan, Andrew and Duquette, Danielle and O'Shea, Donal and Brenner, Michael B. (2016) iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy. Cell Metabolism, 24. pp. 510-519. ISSN 1550-4131

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    Abstract

    Adipose-resident invariant natural killer T (iNKT) cells are key players in metabolic regulation. iNKT cells are innate lipid sensors, and their activation, using their prototypic ligand a-galactosylceramide (aGalCer), induces weight loss and restores glycemic control in obesity. Here, iNKT activation induced fibroblast growth factor 21 (FGF21) production and thermogenic browning of white fat. Complete metabolic analysis revealed that iNKT cell activation induced increased body temperature, V02, VC02, and fatty acid oxidation, without affecting food intake or activity. FGF21 induction played a major role in iNKT cell-induced weight loss, as FGF21 null mice lost significantly less weight after aGalCer treatment. The glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, also activated iNKT cells in humans and mice. In iNKT-deficient mice, liraglutide promoted satiety but failed to induce FGF21, resulting in less weight loss. These findings reveal an iNKT cell-FGF21 axis that defines a new immunemediated pathway that could be targeted for glycemic control and weight regulation.

    Item Type: Article
    Keywords: Glucagon-like; Peptide-1; Killer T-Cells; Alternatively Activated Macrophages; Type-2 Diabetes; Mellitus Innate Lymphoid; Tyrpe-2; White Adipose-Tissues; Invariant NKT Cells; Adaptive Thermogenesis; Antigen Presentation; Energy; Expenditure;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12401
    Identification Number: https://doi.org/10.1016/j.cmet.2016.08.003
    Depositing User: Andrew Hogan
    Date Deposited: 10 Feb 2020 17:40
    Journal or Publication Title: Cell Metabolism
    Publisher: Elsevier
    Refereed: Yes
    URI:

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