摘要：Fibroblast growth factor 21 (FGF21) is a key metabolic regulator with significant potential to treat metabolic disease. Rather than traditional glucose or lipid centric therapies, FGF21 instead functions via expansive remodeling of whole body energy balance [1]. While FGF21's ability to ameliorate disease burden is well established in species ranging from mice to men, the mechanism(s) by which FGF21 is able to instigate the plethora of its in vivo actions have yet to be elucidated. Recently, adipose tissue has emerged as a critical target organ where FGF21 engages its primary receptor complex (FGFR1/KLB) [2, 3]. In fat, FGF21 acts as a metabolic rheostat serving to modulate secretion of adipokines which in turn mediate discrete aspects of FGF21-induced physiology. Supportive of this proposed mode of action is recent evidence demonstrating that adiponectin is not only a biomarker for FGF21 target engagement but is also essential for facilitating some of FGF21s downstream actions [4, 5]. Of critical importance, acute FGF21 signaling is not compromised in Adn./. mice when compared to their WT counterparts. However, only in WT animals with intact adiponectin signaling is FGF21 able to trigger a cascade of metabolic events leading to correction of hyperglycemia and hyperinsulinemia. Correlated with the lack of improvement in glycemia and insulin sensitivity there was also lack of ceramide lowering in FGF21 treated Adn./. animals. Supportive of partitioning of FGF21s metabolic endpoints, weight loss, elevated energy expenditure and reduced circulating lipids were yet evident FGF21-treated Adn./. mice.
