{Reference Type}: Journal Article
{Title}: Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure.
{Author}: Yuan Y;Hu R;Park J;Xiong S;Wang Z;Qian Y;Shi Z;Wu R;Han Z;Ong SG;Lin S;Varady KA;Xu P;Berry DC;Shu G;Jiang Y;
{Journal}: Sci Adv
{Volume}: 10
{Issue}: 26
{Year}: 2024 Jun 28
{Factor}: 14.957
{DOI}: 10.1126/sciadv.adn5229
{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.