Chronic fructose consumption leads to activation of the sterol regulatory element-binding protein 1c (SREBP1c) and the carbohydrate-responsive element-binding protein (ChREBP) that in turn provokes the expression of the liver-derived hormone fibroblast growth factor 21 (FGF21) regulating energy homeostasis and protecting the liver from fructose-induced metabolic disease (Hannou et al., 2018). Here, FGF21 is linked to metabolic disease.