FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Fibroblast growth factor 21 (FGF21) plays a key role in the thermogenic adaptation of white adipose tissue (WAT) to cold exposure. FGF21 is expressed in brown and white adipose tissues and acts in an autocrine/paracrine manner to increase the expression of thermogenic genes, including uncoupling protein 1 (UCP1), in fat tissues. FGF21 enhances PGC-1α protein levels in adipose tissue, which is critical for thermogenesis. FGF21 deficiency impairs the ability of mice to adapt to cold exposure, resulting in reduced browning of WAT. FGF21 treatment increases the appearance of brown-like adipocytes in subcutaneous WAT and enhances the thermogenic capacity of adipose tissues. FGF21 induces thermogenic gene expression in both brown and white adipose tissues, with a significant induction in subcutaneous WAT. FGF21 expression is induced by cold exposure and β-adrenergic stimulation in brown and white adipose tissues. Genetic ablation of FGF21 leads to impaired cold adaptation, reduced thermogenic gene expression, and decreased browning of WAT. PGC-1α is required for the thermogenic effects of FGF21 on adipose tissue. FGF21 regulates PGC-1α at a post-transcriptional level, increasing its protein levels without affecting mRNA expression. FGF21 enhances PGC-1α protein stability, which is essential for thermogenesis. FGF21 plays a critical role in the thermogenic response to cold by activating and expanding the thermogenic machinery in adipose tissues. This process helps to provide a robust defense against hypothermia. FGF21 is a key regulator of metabolic processes and has been shown to improve glucose metabolism and body weight in obese mice. FGF21 may also regulate lipolysis in adipose tissue, although the exact role remains controversial. Overall, FGF21 is essential for the thermogenic adaptation of white adipose tissue to cold exposure and plays a critical role in maintaining energy homeostasis.FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Fibroblast growth factor 21 (FGF21) plays a key role in the thermogenic adaptation of white adipose tissue (WAT) to cold exposure. FGF21 is expressed in brown and white adipose tissues and acts in an autocrine/paracrine manner to increase the expression of thermogenic genes, including uncoupling protein 1 (UCP1), in fat tissues. FGF21 enhances PGC-1α protein levels in adipose tissue, which is critical for thermogenesis. FGF21 deficiency impairs the ability of mice to adapt to cold exposure, resulting in reduced browning of WAT. FGF21 treatment increases the appearance of brown-like adipocytes in subcutaneous WAT and enhances the thermogenic capacity of adipose tissues. FGF21 induces thermogenic gene expression in both brown and white adipose tissues, with a significant induction in subcutaneous WAT. FGF21 expression is induced by cold exposure and β-adrenergic stimulation in brown and white adipose tissues. Genetic ablation of FGF21 leads to impaired cold adaptation, reduced thermogenic gene expression, and decreased browning of WAT. PGC-1α is required for the thermogenic effects of FGF21 on adipose tissue. FGF21 regulates PGC-1α at a post-transcriptional level, increasing its protein levels without affecting mRNA expression. FGF21 enhances PGC-1α protein stability, which is essential for thermogenesis. FGF21 plays a critical role in the thermogenic response to cold by activating and expanding the thermogenic machinery in adipose tissues. This process helps to provide a robust defense against hypothermia. FGF21 is a key regulator of metabolic processes and has been shown to improve glucose metabolism and body weight in obese mice. FGF21 may also regulate lipolysis in adipose tissue, although the exact role remains controversial. Overall, FGF21 is essential for the thermogenic adaptation of white adipose tissue to cold exposure and plays a critical role in maintaining energy homeostasis.