ILC2s are present in adipose tissue and play a critical role in regulating adipose thermogenesis. However, the mechanisms underlying the activation of adipose-resident ILC2s remain poorly defined. Here, we show that IL-33, a potent ILC2 activator, stimulates phosphorylation of AMPK at Thr172 via TAK1 in primary ILC2s, which provides a feedback mechanism to inhibit IL-33–induced NF-κB activation and IL-13 production. Treating ILC2s with adiponectin or an adiponectin receptor agonist (AdipoRon) activated AMPK and decreased IL-33–NF-κB signaling. AdipoRon also suppressed cold-induced thermogenic gene expression and energy expenditure in vivo. In contrast, adiponectin deficiency increased the ILC2 fraction and activation, leading to up-regulated thermogenic gene expression in adipose tissue of cold-exposed mice. ILC2 deficiency or blocking ILC2 function by neutralization of the IL-33 receptor with anti-ST2 diminished the suppressive effect of adiponectin on cold-induced adipose thermogenesis and energy expenditure. Taken together, our study reveals that adiponectin is a negative regulator of ILC2 function in adipose tissue via AMPK-mediated negative regulation of IL-33 signaling.
Skip Nav Destination
Close
Article navigation
Article|
October 26 2020
Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling
Lu Wang,
Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
3
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for other works by this author on:
Yan Luo,
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
2
Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Central South University, Changsha, Hunan, China
Search for other works by this author on:
Liping Luo,
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Dandan Wu,
Data curation, Formal analysis, Investigation, Project administration, Validation, Visualization
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Xiaofeng Ding,
Xiaofeng Ding
Investigation, Methodology
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Handong Zheng,
Handong Zheng
Methodology, Resources, Visualization
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Haisha Wu,
Haisha Wu
Investigation
3
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for other works by this author on:
Bilian Liu,
Bilian Liu
Investigation
2
Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Central South University, Changsha, Hunan, China
Search for other works by this author on:
Xin Yang,
Xin Yang
Investigation, Project administration, Resources
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Floyd Silva,
Floyd Silva
Formal analysis, Investigation, Project administration, Resources, Visualization, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Chunqing Wang,
Chunqing Wang
Data curation, Resources
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Xing Zhang,
Xing Zhang
Investigation
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Xianyun Zheng,
Xianyun Zheng
Investigation
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Jindong Chen,
Jindong Chen
Project administration
3
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for other works by this author on:
Jonathan Brigman,
Jonathan Brigman
Methodology, Supervision
6
Department of Neuroscience, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Michael Mandell,
Michael Mandell
Methodology, Resources, Writing - review & editing
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
5
Autophagy, Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM
Search for other works by this author on:
Zhiguang Zhou,
Zhiguang Zhou
Data curation, Investigation, Project administration, Resources, Writing - review & editing
2
Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Central South University, Changsha, Hunan, China
Search for other works by this author on:
Feng Liu,
Feng Liu
Conceptualization, Writing - review & editing
7
Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX
Search for other works by this author on:
Xuexian O. Yang,
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
5
Autophagy, Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM
Xuexian O. Yang: xyang@salud.unm.edu
Search for other works by this author on:
Meilian Liu
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
5
Autophagy, Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM
Correspondence to Meilian Liu: meilianliu@salud.unm.edu
Search for other works by this author on:
Lu Wang
Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
3
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Yan Luo
Formal analysis, Investigation, Methodology, Visualization
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
2
Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Central South University, Changsha, Hunan, China
Liping Luo
Data curation, Formal analysis, Writing - original draft, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Dandan Wu
Data curation, Formal analysis, Investigation, Project administration, Validation, Visualization
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
Xiaofeng Ding
Investigation, Methodology
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Handong Zheng
Methodology, Resources, Visualization
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
Haisha Wu
Investigation
3
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Bilian Liu
Investigation
2
Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Central South University, Changsha, Hunan, China
Xin Yang
Investigation, Project administration, Resources
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Floyd Silva
Formal analysis, Investigation, Project administration, Resources, Visualization, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Chunqing Wang
Data curation, Resources
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Xing Zhang
Investigation
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Xianyun Zheng
Investigation
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
Jindong Chen
Project administration
3
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Jonathan Brigman
Methodology, Supervision
6
Department of Neuroscience, University of New Mexico Health Sciences Center, Albuquerque, NM
Michael Mandell
Methodology, Resources, Writing - review & editing
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
5
Autophagy, Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM
Zhiguang Zhou
Data curation, Investigation, Project administration, Resources, Writing - review & editing
2
Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Central South University, Changsha, Hunan, China
Feng Liu
Conceptualization, Writing - review & editing
7
Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX
Xuexian O. Yang
Conceptualization, Methodology, Writing - review & editing
4
Department of Microbiology and Molecular Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM
5
Autophagy, Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM
Meilian Liu
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM
5
Autophagy, Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM
*
L. Wang, Y. Luo, L. Luo, and D. Wu contributed equally to this paper.
Xuexian O. Yang: xyang@salud.unm.edu
Correspondence to Meilian Liu: meilianliu@salud.unm.edu
Received:
June 11 2019
Revision Received:
October 20 2019
Accepted:
September 01 2020
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding:
American Diabetes Association
(1-17-IBS-261)
American Heart Association
(18CDA34110228)
National Institute of Diabetes and Digestive and Kidney Diseases
(DK110439)
University of New Mexico
(P30GM103400, AI142200, NO AWARD)
© 2020 Wang et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2021) 218 (2): e20191054.
Article history
Received:
June 11 2019
Revision Received:
October 20 2019
Accepted:
September 01 2020
Citation
Lu Wang, Yan Luo, Liping Luo, Dandan Wu, Xiaofeng Ding, Handong Zheng, Haisha Wu, Bilian Liu, Xin Yang, Floyd Silva, Chunqing Wang, Xing Zhang, Xianyun Zheng, Jindong Chen, Jonathan Brigman, Michael Mandell, Zhiguang Zhou, Feng Liu, Xuexian O. Yang, Meilian Liu; Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling. J Exp Med 1 February 2021; 218 (2): e20191054. doi: https://doi.org/10.1084/jem.20191054
Download citation file:
Close
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
838
Views
0
Citations
Advertisement