Figure 1.

Fibroblast growth factor 21 as a stress hormone acting via a tissue-adipocyte communication axis. Stressed tissues through induction of FGF21 (left box) alert adipocytes by activating the adipocyte FGFR1-KLB complex (center box). Adipocytes respond with secretory metabolic products and adipokines that alleviate tissue-specific stress through modification of cellular pathways whose alterations (right box) are a potentially destructive result of systemic or internal cellular stress (left box). Systemic FGF21 acts on adipocytes in major adipose depots or in the microenvironment of peripheral tissues. Breast is shown as an example of the latter. FGF21-induced adipocyte secretory products, such as adiponectin, leptin, and free fatty acids (FFAs), act both systemically or in the local microenvironment (center box) to affect stressed organs or parenchymal cells, respectively.