Peer-Reviewed Journal Details
Mandatory Fields
Lynch, L;Hogan, AE;Duquette, D;Lester, C;Banks, A;LeClair, K;Cohen, DE;Ghosh, A;Lu, B;Corrigan, M;Stevanovic, D;Maratos-Flier, E;Drucker, DJ;O'Shea, D;Brenner, M
2016
September
Cell Metabolism
iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy
Published
4 ()
Optional Fields
GLUCAGON-LIKE PEPTIDE-1 KILLER T-CELLS ALTERNATIVELY ACTIVATED MACROPHAGES TYPE-2 DIABETES-MELLITUS INNATE LYMPHOID TYPE-2 WHITE ADIPOSE-TISSUES INVARIANT NKT CELLS ADAPTIVE THERMOGENESIS ANTIGEN PRESENTATION ENERGY-EXPENDITURE
24
510
519
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 alpha-galactosylceramide (alpha GalCer), 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 immune-mediated pathway that could be targeted for glycemic control and weight regulation.
CAMBRIDGE
1550-4131
10.1016/j.cmet.2016.08.003
Grant Details