Products Cited in Publications Worldwide Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure

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

Yexian Yuan; Ruoci Hu; Jooman Park; Shaolei Xiong; Zilai Wang; Yanyu Qian; Zuoxiao Shi; Ruifan Wu; Zhenbo Han; Sang-Ging Ong; Shuhao Lin; Krista A. Varady; Pingwen Xu; Daniel C. Berry; Gang Shu; Yuwei Jiang

DOI: PMID:

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.

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AZD2098

A924249566203-88-199%

AZD2098

14.0/1mg

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