The study investigates the role of fibroblast growth factor 21 (FGF21) in the thermogenic recruitment of white adipose tissues (WATs) during adaptive thermogenesis. FGF21 is shown to play a physiological role in increasing the expression of uncoupling protein 1 (UCP1) and other thermogenic genes in fat tissues, particularly in subcutaneous inguinal WAT (IWAT) and perirenal WAT (PRWAT). FGF21 acts in an autocrine/paracrine manner to enhance PGC-1α protein levels, which are crucial for thermogenic gene expression. Genetic ablation of FGF21 in mice results in impaired adaptation to cold exposure, with reduced browning of WAT and diminished expression of thermogenic genes. The study concludes that FGF21 acts to activate and expand the thermogenic machinery in vivo, providing a robust defense against hypothermia.The study investigates the role of fibroblast growth factor 21 (FGF21) in the thermogenic recruitment of white adipose tissues (WATs) during adaptive thermogenesis. FGF21 is shown to play a physiological role in increasing the expression of uncoupling protein 1 (UCP1) and other thermogenic genes in fat tissues, particularly in subcutaneous inguinal WAT (IWAT) and perirenal WAT (PRWAT). FGF21 acts in an autocrine/paracrine manner to enhance PGC-1α protein levels, which are crucial for thermogenic gene expression. Genetic ablation of FGF21 in mice results in impaired adaptation to cold exposure, with reduced browning of WAT and diminished expression of thermogenic genes. The study concludes that FGF21 acts to activate and expand the thermogenic machinery in vivo, providing a robust defense against hypothermia.