and triglyceride formation [6], [15]. Although, both liver and adipose tissue may participate in the pharmacological action of FGF21, the degree and nature of their contributions may differ. FGF21 has a 10-fold higher affinity to induce ERK-phosphorylation in adipose tissue than in liver, suggesting that FGF21 may preferentially target adipose tissue [15]. In addition, we observed that FGF21 acutely reduces blood glucose and insulin levels while it had no effect on cholesterol or triglyceride levels [15], thus FGF21 may induce separable responses on glucose and lipid homeostasis. The fact that FGF21 improves adiposity, lipid and glucose metabolism in a tissue-restricted manner and increases glucose uptake acutely in adipose tissues [15] prompted us to test whether the β-klotho expressing tissue, WAT, was necessary for FGF21 to elicit efficacy. [15].