7030B-C5 regulates glucose metabolism through FoxO1. (a) Male ApoE KO mice were intragastrically injected with vehicle and 7030B-C5 (10 mg/kg per day, 30 mg/kg per day), respectively, for 12 weeks. At the end of experiment, liver samples were collected. The liver lipid accumulation was determined by Oil-Red-O staining and quantified by using ImageJ. a, chow; b, HFD; c, 7030B-C5 (10 mg/kg); d, 7030B-C5 (30 mg/kg). Scale bar = 500 μm. Representative images are shown. (b) Volcano plots for all differentially expressed genes in comparison. Horizontal coordinate is the value of fold change between 7030B-C5 group/HFD difference genes and the vertical coordinates is the p value. The left side represents the differentially down-regulated gene, the right side represents the differentially up-regulated gene, and the green and red dots represent the differential gene p < 0.05, blank dots represent the non-significantly differential gene. (c) GO pathway enrichment analysis of 321 differentially expressed genes. (d) KEGG pathway enrichment analysis of 42 differentially expressed genes involved in glucose and lipid metabolism. (e) Male ApoE KO mice were intragastrically injected with vehicle and 7030B-C5 (10 mg/kg per day, 30 mg/kg per day), respectively, for 12 weeks. At the end of experiment, triglycerides, glucose, glycated serum protein (GSP) and glycated albumin (GA) in the serum were collected from the ApoE KO mice at the 12th week after 7030B-C5 treatment. (f) Effects of 7030B-C5 on FoxO1 expression in HepG2 cells. HepG2 cells were treated with 7030B-C5 in a series of concentrations for 24 h. Expression of FoxO1 protein was measured by Western blot. (g) The interaction of FoxO1 with IRE element was determined by luciferase reporter system. (h) HepG2 cells were treated with 7030B-C5 in a series of concentrations for 24 h. The mRNA level of PEPCK, G6Pase, MTP and ApoC-III was measured by RT-qPCR analysis. Values are presented as means ± SEM (n = 10 per group). *p < 0.05 vs. control in the corresponding group. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)