| First Author | Yuan Y | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 26 | Pages | eadn5229 |
| PubMed ID | 38924414 | Mgi Jnum | J:350242 |
| Mgi Id | MGI:7661946 | Doi | 10.1126/sciadv.adn5229 |
| Citation | Yuan Y, et al. (2024) Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure. Sci Adv 10(26):eadn5229 |
| abstractText | 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. |
