(A) Klb mRNA levels in epididymal WAT (eWAT), subcutaneous WAT (scWAT), interscapular BAT, and liver of 12–13 week old wild-type (WT) and β-klotho adipose-specific knockout mice (KLB AdipoKO) (n = 6/group). (B) Western blot analysis of phospho-ERK1/2 and total ERK1/2 levels from eWAT of 12–13 week old WT and KLB AdipoKO mice administered vehicle (Veh) or FGF21 (1 mg/kg) for 15 minutes. (C) Percent change in plasma glucose levels in lean, 12–14 week old, male KLB AdipoKO mice and WT littermate controls co-injected with insulin and either vehicle or FGF21 (1 mg/kg) (n = 6/group). (D) Percent change in plasma glucose levels in 16–18 week old male, diet-induced obese (DIO) KLB AdipoKO mice and WT littermate controls on co-injected with insulin and either vehicle or FGF21 (1 mg/kg) (n = 5-6/group). Plasma adiponectin levels at the indicated time points in (E) 12–13 week old, chow-fed male WT (KLBfl/fl) and (F) DIO 16–18 week old male WT (KLBfl/fl) mice on high fat diet for 12 weeks after i.p. administration of vehicle or FGF21 (1 mg/kg) (n = 8/group). (G) Percent change in plasma glucose levels in 12–14 week old, male WT (+/+ and +/−) and Adiponectin knockout (Adipoq KO) littermates co-injected with insulin and either vehicle or FGF21 (1 mg/kg) (n = 6/group). Values are mean +/− SEM. (*, P< 0.05; **, P<0.01; ***, P< 0.005; and #, P<0.001).