Fig. 6.

AdipoRonPEG₅ contributes to the regulation of glucose and lipid metabolism in the liver. A–C: Wild-type mice were fed high-fat diet for 4 weeks and treated with AdipoRonPEG₅ (5 mg/kg) twice a day for 5 days before the harvest liver. One or two samples were pooled for 1 RNAseq sample in each group. A: Hierarchical clustering of transcriptional profiles in AdipoRon and AdipoRonPEG₅-treated liver. The genes were divided into nine groups dependent on the response of gene expression to AdipoRonPEG₅ and AdipoRon treatment. Three kinds of response (up, nc and down) and two kinds of treatment produce nine groups. The criteria of grouping are as follows. Down: fold change < 0.9, nc: 0.9 < fold change < 1.1, up: fold change > 1.1. Right column exhibits the proportion of each group. B: Principal component analysis of whole transcriptomes from all samples. C: 3522 AdipoRonPEG₅ specifically downregulated genes (Set 1) were identified dependent on hierarchical clustering. Fifteen most enriched pathway by gene ontology (GO) pathway analysis shows the characteristics of genes that were specifically downregulated in AdipoRonPEG₅ treated liver. D: Volcano plot comparing transcriptomes from AdipoRon-treated group versus AdipoRonPEG₅-treated group. Metabolism related genes that is at least significantly changed (Log₁₀ (P value) < −1.3) are annotated. The number of genes that were significantly downregulated (blue) or upregulated (red) are described at the bottom. E: Hierarchical clustering of genes involved in gluconeogenesis-related genes. F: Hierarchical clustering of genes related to AdipoR1 and AdipoR2 signaling pathway. G: The most upregulated genes by AdipoRon (left panel) and AdipoRonPEG5 (right panel) in the liver. H: The most downregulated genes by AdipoRon (left panel) and AdipoRonPEG5 (right panel) in the liver.