Fibroblast growth factor 21 (FGF21) regulates energy homeostasis in mammals [1], [2]. It is expressed predominantly in liver, white and brown adipose tissues (WAT & BAT) and pancreas [3]. In response to fasting or a ketogenic diet, FGF21 expression is induced primarily in the liver through the action of PPARα [4], [5]. Pharmacologically, FGF21 has become recognized as a modulator of glucose and lipid homeostasis in vivo [1], [6]. Recombinant FGF21 therapy corrected many metabolic perturbations in diseased rodent models and non-human primates [1], [6], [7]. In these different models, FGF21 reduced body weight, plasma and hepatic cholesterol and triglycerides levels, and increased oxygen consumption [1], [6]. Additionally, FGF21 improved the diabetic phenotypes of these animals by decreasing hyperglycemia, hyperinsulinemia, glucose intolerance, and increasing peripheral and hepatic insulin sensitivity [7]. Generation of FGF21 null mice confirmed the essential role of FGF21 in metabolic physiology [8], [9]. Mild obesity and adipocyte hypertrophy were observed in KO mice, indicating a crucial function for FGF21 in adipose tissue biology [8], [9].
