IL-27 signalling promotes adipocyte thermogenesis and energy expenditure

Qian Wang^#^{1

2}, Dehai Li^#^{1

2}, Guangchao Cao^#^{1

2}, Qiping Shi^#³, Jing Zhu^{1

2}, Mingyue Zhang^{1

2}, Hao Cheng⁴, Qiong Wen^{1

2}, Hao Xu⁵, Leqing Zhu^{2

6}, Hua Zhang^{1

2}, Rachel J Perry^{7

8}, Olga Spadaro^{5

9}, Yunfan Yang⁹, Shengqi He¹⁰, Yong Chen¹⁰, Baocheng Wang¹¹, Guangqiang Li^{2

6}, Zonghua Liu^{1

2}, Caixian Yang¹², Xiaoli Wu¹³, Libing Zhou¹⁴, Qinghua Zhou^{1

2}, Zhenyu Ju¹⁵, Hongyun Lu¹, Yongjie Xin¹, Xiaoyong Yang^{8

9}, Cunchuan Wang¹⁶, Yong Liu¹⁰, Gerald I Shulman^{7

8}, Vishwa Deep Dixit^{5

9}, Ligong Lu¹⁷, Hengwen Yang^{18

19}, Richard A Flavell²⁰, Zhinan Yin^{21

22}

Affiliations

¹ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
² The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China.
³ Department of Endocrine, The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
⁶ The First Affiliated Hospital, Faculty of Medical Science, Jinan University, Guangzhou, China.
⁷ Department of Medicine, School of Medicine, Yale University, New Haven, CT, USA.
⁸ Department of Cellular & Molecular Physiology, School of Medicine, Yale University, New Haven, CT, USA.
⁹ Department of Comparative Medicine, School of Medicine, Yale University, New Haven, CT, USA.
¹⁰ Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan, China.
¹¹ Tsinghua Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China.
¹² Department of Endocrine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
¹³ School of Life Sciences, Tianjin University, Tianjin, China.
¹⁴ Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
¹⁵ Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China.
¹⁶ Department of Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
¹⁷ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China. lu_ligong@163.com.
¹⁸ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China. hengwenyang@jnu.edu.cn.
¹⁹ The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China. hengwenyang@jnu.edu.cn.
²⁰ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA. richard.flavell@yale.edu.
²¹ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China. tzhinan@jnu.edu.cn.
²² The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China. tzhinan@jnu.edu.cn.

^# Contributed equally.

PMID: 34819664
DOI: 10.1038/s41586-021-04127-5

IL-27 signalling promotes adipocyte thermogenesis and energy expenditure

Qian Wang et al. Nature. 2021 Dec.

. 2021 Dec;600(7888):314-318.

doi: 10.1038/s41586-021-04127-5. Epub 2021 Nov 24.

Authors

Affiliations

¹ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
² The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China.
³ Department of Endocrine, The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
⁶ The First Affiliated Hospital, Faculty of Medical Science, Jinan University, Guangzhou, China.
⁷ Department of Medicine, School of Medicine, Yale University, New Haven, CT, USA.
⁸ Department of Cellular & Molecular Physiology, School of Medicine, Yale University, New Haven, CT, USA.
⁹ Department of Comparative Medicine, School of Medicine, Yale University, New Haven, CT, USA.
¹⁰ Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan, China.
¹¹ Tsinghua Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China.
¹² Department of Endocrine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
¹³ School of Life Sciences, Tianjin University, Tianjin, China.
¹⁴ Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
¹⁵ Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China.
¹⁶ Department of Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
¹⁷ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China. lu_ligong@163.com.
¹⁸ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China. hengwenyang@jnu.edu.cn.
¹⁹ The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China. hengwenyang@jnu.edu.cn.
²⁰ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA. richard.flavell@yale.edu.
²¹ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China. tzhinan@jnu.edu.cn.
²² The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China. tzhinan@jnu.edu.cn.

^# Contributed equally.

PMID: 34819664
DOI: 10.1038/s41586-021-04127-5

Abstract

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes^1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized^3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

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References

1. Betz, M. J. & Enerback, S. Human brown adipose tissue: what we have learned so far. Diabetes 64, 2352–2360 (2015). - DOI
1. Bartelt, A. & Heeren, J. Adipose tissue browning and metabolic health. Nat. Rev. Endocrinol. 10, 24–36 (2014). - DOI
1. Wang, W. & Seale, P. Control of brown and beige fat development. Nat. Rev. Mol. Cell Biol. 17, 691–702 (2016). - DOI
1. Odegaard, J. I. et al. Perinatal licensing of thermogenesis by IL-33 and ST2. Cell 166, 841–854 (2016). - DOI
1. Qiu, Y. et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157, 1292–1308 (2014). - DOI

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IL-27 signalling promotes adipocyte thermogenesis and energy expenditure

Affiliations

IL-27 signalling promotes adipocyte thermogenesis and energy expenditure

Authors

Affiliations

Abstract

References

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