Adiponectin Enhances Cold-Induced Browning of Subcutaneous Adipose Tissue via Promoting M2 Macrophage Proliferation

Adiponectin is an abundant adipokine with pleiotropic protective effects against a cluster of obesity-related cardiometabolic disorders. However, its role in adaptive thermogenesis has scarcely been explored. Here we showed that chronic cold exposure led to a markedly elevated production of adiponectin in adipocytes of subcutaneous white adipose tissue (scWAT), which in turn bound to M2 macrophages in the stromal vascular fraction. Chronic cold exposure-induced accumulation of M2 macrophages, activation of beige cells, and thermogenic program were markedly impaired in scWAT of adiponectin knockout (ADN KO) mice, whereas these impairments were reversed by replenishment with adiponectin. Mechanistically, adiponectin was recruited to the cell surface of M2 macrophages via its binding partner T-cadherin and promoted the cell proliferation by activation of Akt, consequently leading to beige cell activation. These findings uncover adiponectin as a key efferent signal for cold-induced adaptive thermogenesis by mediating the crosstalk between adipocytes and M2 macrophages in scWAT.