Activation of classical brown adipose tissues (BAT) and/or augmentation ofbrowning (beiging) in white adipose tissue (WAT) have recently emerged as a potential therapeutic strategy to combat obesity and its related metabolic complications. However, how neurological and immunological signals communicate with each other to coordinate the activation of classical BAT and browning of WAT remains poorly understood. We found several adipokines secreted from adipocytes, including adiponectin, FGF21 and adipocyte-fatty acid binding protein (A-FABP) act in an autocrine/paracrine manner to participate in the adaptive thermogenesis in BAT and WAT by crosstalk with sympathetic nerve system and thyroid hormones. A-FABP enhances the activation of classical BAT by acting as a lipid-binding chaperone to transport free fatty acids released from WAT into BAT for fatty acid oxidation, and also by promoting the conversion of thyroid hormones from its inactive form T4 to active form T3 through induction of type-II iodothyronine deiodinase in BAT. On the other hand, FGF21 and adiponectin enhance the browning and thermogenesis of WAT by creating a favorable immunological environment required for the biogenesis of beige adipocytes. In response to chronic cold challenge, activated sympathetic nerves send the signals to mature adipocytes for production of FGF21, which in turn acts in an autocrine manner to stimulate secretion of the chemokine CCL11, thereby promoting biogenesis of beige adipocytes through recruitment of type-2 immune cells. On the other hand, sympathetic nerve signals can also act on lymph nodes to promote the release of IL3 for beiging of WAT. These findings suggest neurological and immunological systems crosstalk at multiple levels to coordinate cold-induced activation of classical BAT andbrowning of WAT, thereby maintaining energy homeostasis during cold stress through adaptive thermogensis.