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

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.

Citation

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. Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure. Science advances. 2024 Jun 28;10(26):eadn5229

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PMID: 38924414

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