E2F8 promotes hepatic steatosis through FABP3 expression in diet-induced obesity in zebrafish.

BACKGROUND: Diet-induced hepatic steatosis is highly associated with nonalcoholic fatty liver disease, which is related to the development of metabolic syndrome. While advanced stage nonalcoholic hepatic steatosis and steatohepatitis (NASH) result ultimately in fibrosis and cirrhosis, the molecular basis for lipid droplet formation is poorly understood. Common pathways underlie the pathology of mammalian obesity and the zebrafish diet-induced obesity model (DIO-zebrafish) used in this study. METHODS: Our analysis involved a combination of transcriptome (DNA microarray) and proteome (two-dimensional electrophoresis) methods using liver tissue from DIO-zebrafish to find candidate genes involved in hepatic steatosis. We conducted intraperitoneal injection (i.p.) of morpholino antisense oligonucleotides (MOs) for each gene into DIO-zebrafish. We also conducted in vitro overexpression in human cells. Additionally, we examined gene expression during feeding experiments involving anti-obesity compounds, creatine and anserine. RESULTS: We found that fatty acid binding protein 3 (fabp3) and E2F transcription factors were upregulated in hepatic steatosis. E2f8 MO i.p. suppressed fabp3 expression in liver, and ameliorated hepatic steatosis. In human cells (HepG2), E2F8 overexpression promoted FABP3 expression. Additionally, co-administration of creatine and anserine suppressed obesity associated phenotypes including hepatic steatosis as indicated by e2f8 and fabp3 down regulation. CONCLUSION: We discovered that the e2f8-fabp3 axis is important in the promotion of hepatic steatosis in DIO-zebrafish. The combination of transcriptome and proteome analyses using the disease model zebrafish allow identification of novel pathways involved in human diseases.

The usefulness of the collagen and elastin sponge derived from salmon as an artificial dermis and scaffold for tissue engineering.

Collagen sponge is one of the medical materials that are frequently used in clinical medicine. However, the problem of prion disease harmfully affected the usage of mammals-derived medical materials. Since there have been no reports about prion disease occurring in marine products, we produced the collagen and elastin sponge (CES) made from salmon, and investigated whether the CES could be a substitute for mammalian collagen sponge. Fibroblasts were seeded in the CES to examine whether the CES could be used as a scaffold for tissue engineering. The results of the WST-1 assay showed that the fibroblasts were viable and were well proliferated in the CES. To examine whether the CES could be used as an artificial dermis, the CES and TERUDERMIS (traditional collagen sponge) were grafted onto the skin defects on the dorsum of rats. The histological findings of these ulcers showed non-significant difference between the CES and TERUDERMIS. Because of the safety, the abundance of the resources, and the possessing same ability as TERUDERMIS, the biomedical materials derived from marine products may be a substitute for those derived from mammals.