Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure-Reference-Cited by-同舟云学术

Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure

Published:2024-06-28 Issue:26 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Yuan Yexian¹²^ORCID,Hu Ruoci¹³^ORCID,Park Jooman¹^ORCID,Xiong Shaolei¹^ORCID,Wang Zilai⁴,Qian Yanyu¹,Shi Zuoxiao¹³,Wu Ruifan¹⁵^ORCID,Han Zhenbo⁶,Ong Sang-Ging⁶⁷^ORCID,Lin Shuhao⁸,Varady Krista A.⁸,Xu Pingwen⁹^ORCID,Berry Daniel C.¹⁰^ORCID,Shu Gang⁵^ORCID,Jiang Yuwei¹³⁹^ORCID

Affiliation:

1. Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

2. Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China.

3. Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.

4. Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA.

5. Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Province Key Laboratory of Animal Nutritional Regulation and National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.

6. Department of Pharmacology and Regenerative Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

7. Division of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

8. Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.

9. Division of Endocrinology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

10. Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.

Abstract

There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived C-C motif chemokine (CCL22) into iWAT. CCL22 injection into iWAT effectively promotes iWAT beiging, while blocking CCL22 with antibodies can prevent it. Mechanistically, the CCL22 receptor, C-C motif chemokine receptor 4 (CCR4), within eosinophils and its downstream focal adhesion kinase/p65/interleukin-4 signaling are essential for CCL22-mediated beige adipocyte formation. Moreover, CCL22 levels are inversely correlated with body weight and fat mass in mice and humans. Acute elevation of CCL22 levels effectively prevents diet-induced body weight and fat gain by enhancing adipose beiging. Together, our data identify the CCL22-CCR4 axis as an essential mediator for LN-controlled adaptive thermogenesis and highlight its potential to combat obesity and its associated complications.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adn5229

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