Endocrine FGF21 secreted by the liver is required for the metabolic actions of JNK signaling in adipocytes. (A,B) ADWT, ADKO, and ADKOΔFgf21 mice were fed a HFD (16 wk). The circulating concentration of adiponectin was measured by ELISA (mean ± SEM; n = 7∼8). (**) P < 0.01. The expression of Adipoq mRNA by IngF was measured by TaqMan assay (mean ± SEM; n = 7). (*) P < 0.05; (**) P < 0.01. (C,D) Mice were treated with AAV8-TBG-Cre and fed a HFD (16 wk). The circulating concentration of adiponectin was measured by ELISA (mean ± SEM; n = 6). (*) P < 0.05; (**) P < 0.01. The expression of Adipoq mRNA by IngF was measured by TaqMan assay (mean ± SEM; n = 6∼7). (**) P < 0.01. (E) The blood concentration of FGF21 in ND-fed and HFD-fed (16 wk) ADWTΔAdq and ADKOΔAdq mice was measured by ELISA (mean ± SEM; n = 6∼10). (F–H) The expression of Fgf21, Fgfr1, and Klb by IngF and liver was measured by TaqMan assays (mean ± SEM; n = 6∼8). (**) P < 0.01. (I) Whole body mass of ND-fed and HFD-fed (16 wk) mice was measured (mean ± SEM; n = 6∼11). (J,K) Tolerance tests for glucose (GTT) and insulin (ITT) were performed using ND-fed and HFD-fed (16-wk) mice (mean ± SEM; n = 8∼11). (L) The fasted blood glucose concentration was measured (mean ± SEM; n = 8∼11). (M) Sections prepared from IngF and liver were stained with H&E. Scale bar, 100 µm.