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

Lydia Lynch; Andrew E. Hogan; Danielle Duquette; Chantel Lester; Alexander Banks; Katherine LeClair; David E. Cohen; Abhisek Ghosh; Bing Lu; Michelle Corrigan; Darko Stevanovic; Eleftheria Maratos-Flier; Daniel J. Drucker; Donal O'Shea; Michael Brenner

doi:10.1016/j.cmet.2016.08.003

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

Lydia Lynch, Andrew E. Hogan, Danielle Duquette, Chantel Lester, Alexander Banks, Katherine LeClair, David E. Cohen, Abhisek Ghosh, Bing Lu, Michelle Corrigan, Darko Stevanovic, Eleftheria Maratos-Flier, Daniel J. Drucker, Donal O'Shea, Michael Brenner

Research output: Contribution to journal › Article › peer-review

142 Scopus citations

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 α-galactosylceramide (αGalCer), 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 αGalCer 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.

Original language	English (US)
Pages (from-to)	510-519
Number of pages	10
Journal	Cell Metabolism
Volume	24
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2016.08.003
State	Published - Sep 13 2016
Externally published	Yes

All Science Journal Classification (ASJC) codes

Physiology
Molecular Biology
Cell Biology

Access to Document

10.1016/j.cmet.2016.08.003

Cite this

Lynch, L., Hogan, A. E., Duquette, D., Lester, C., Banks, A., LeClair, K., Cohen, D. E., Ghosh, A., Lu, B., Corrigan, M., Stevanovic, D., Maratos-Flier, E., Drucker, D. J., O'Shea, D., & Brenner, M. (2016). iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy. Cell Metabolism, 24(3), 510-519. https://doi.org/10.1016/j.cmet.2016.08.003

@article{f58b1aec4ab94661ae3465d97e777e50,

title = "iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy",

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 α-galactosylceramide (αGalCer), 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 αGalCer 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.",

author = "Lydia Lynch and Hogan, {Andrew E.} and Danielle Duquette and Chantel Lester and Alexander Banks and Katherine LeClair and Cohen, {David E.} and Abhisek Ghosh and Bing Lu and Michelle Corrigan and Darko Stevanovic and Eleftheria Maratos-Flier and Drucker, {Daniel J.} and Donal O'Shea and Michael Brenner",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = sep,

day = "13",

doi = "10.1016/j.cmet.2016.08.003",

language = "English (US)",

volume = "24",

pages = "510--519",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "3",

}

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, 'iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy', Cell Metabolism, vol. 24, no. 3, pp. 510-519. https://doi.org/10.1016/j.cmet.2016.08.003

TY - JOUR

T1 - iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy

AU - Lynch, Lydia

AU - Hogan, Andrew E.

AU - Duquette, Danielle

AU - Lester, Chantel

AU - Banks, Alexander

AU - LeClair, Katherine

AU - Cohen, David E.

AU - Ghosh, Abhisek

AU - Lu, Bing

AU - Corrigan, Michelle

AU - Stevanovic, Darko

AU - Maratos-Flier, Eleftheria

AU - Drucker, Daniel J.

AU - O'Shea, Donal

AU - Brenner, Michael

PY - 2016/9/13

Y1 - 2016/9/13

N2 - 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 α-galactosylceramide (αGalCer), 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 αGalCer 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.

AB - 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 α-galactosylceramide (αGalCer), 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 αGalCer 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.

UR - http://www.scopus.com/inward/record.url?scp=84990848453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990848453&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2016.08.003

DO - 10.1016/j.cmet.2016.08.003

M3 - Article

C2 - 27593966

AN - SCOPUS:84990848453

SN - 1550-4131

VL - 24

SP - 510

EP - 519

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this