Fig. 5.

AdipoRonPEG₅ activates AMPK signaling and reduces ceramide species in vivo. A: Liver and subcutaneous adipose tissue were harvested after single treatment of AdipoRon or AdipoRonPEG₅. Representative images of the western blot for phosphorylation of AMPK and ACC (n = 4). B–L: Wild-type mice were fed high-fat diet for 4 weeks and treated with AdipoRon or AdipoRonPEG5 (5 mg/kg) twice a day for 5 days before harvesting tissues. RNAseq of liver derived RNA and mass spectrometry analysis of ceramides were performed. B: Heatmap of the genes involved in ceramidase activity. C–L: Sphingoid bases and dihydroceramide species fold-change levels in the liver, pancreas, subcutaneous adipose tissue (C–H), and serum (I–L, fold-change between D0 and D5 were indicated on the graph) were determined by mass spectrometry (n = 5). Data were analyzed by two-way ANOVA with Tukey's test. Data are mean ± SEM. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001 and ∗∗∗∗P < 0.0001.