[Improvement situation on indexes of the zebrafish disease model of non-alcoholic fatty liver disease with FGF21 analogues].

Objective: To detect the therapeutic efficacy of FGF21 analogues on the zebrafish model of non-alcoholic fatty liver disease. Methods: A zebrafish model of non-alcoholic fatty liver disease was established by providing the normal diet fed to wild-type zebrafish three times daily. PF-05231023 was administered exogenously at a final concentration of 0.5 µmol/L. Body length, body weight, triglycerides, and other indexes were measured after 20 days. Pathological changes were evaluated in liver tissue sections by HE staining. Quantitative PCR was used to identify expressional changes in genes related to lipid metabolism, endoplasmic reticulum stress, and inflammation. Results: QPCR and immunofluorescence staining results showed that FGF21 was highly expressed in the zebrafish model group. The addition of the FGF21 analogue PF-05231023 significantly reduced the body length and body weight (P < 0.01), and the triglyceride content (P < 0.05) in the zebrafish model group. The liver HE staining results showed that PF-05231023 had alleviated the large and tiny bullae fat, lesions, and others in the zebrafish model group. The quantitative PCR results demonstrated that PF-05231023 reduced the expression of lipogenic factors (P < 0.01), inflammatory-related factors (P < 0.001), and genes related to endoplasmic reticulum stress (P < 0.05), but raised lipid-oxidation-related factors (P < 0.05) in the zebrafish model group. The addition of PF-05231023 reduced oleic acid-induced lipid and triglyceride levels in HepG2 cells. Conclusion: FGF21 analogue addition can improve indexes in the zebrafish disease model of non-alcoholic fatty liver disease.

[Establishment of zebrafish model for non-alcoholic steatohepatitis].

Objective: To establish overfed zebrafish model for non-alcoholic steatohepatitis. Methods: The wild-type zebrafish was fed 3 times a day with normal diet. Body length, weight, and triglyceride levels were measured after 20 days of feeding. The changes in expression of genes associated with cholesterol metabolism, lipid metabolism, endoplasmic reticulum stress, and inflammation were detected by quantitative PCR. Liver tissue sections were stained with H&E. Statistical analyses between groups were compared using t-test. Results: The body length (0.71±0.014) cm and body weight (44.83±1.833) mg of model group were higher than that of control group (0.50±0.009) cm and body weight (19.33±2.753) mg (total (body length) = 12.36, total (body weight) = 7.71, P < 0.01). Triglyceride content in the model group was (59.15 ± 0.5612) µmol / L, higher than the control group (16.71 ± 0.3562) µmol / L (t = 63.84, P < 0.001). Quantitative PCR results showed that the expression of genes related to cholesterol synthesis in the model group was higher than that in the control group (P < 0.01). The expression levels of lipid production and lipid oxidation related factors in the model group were higher than the control group. The difference between the two groups was statistically significant (P < 0.05). The expression of inflammation-related factors in the model group was higher than that in the control group (P < 0.001), and the expression of genes related to endoplasmic reticulum stress in the model group was higher than that to control group (P<0.001). Liver H&E staining showed that the model group had pathological changes such as large bulla and vesicles compared to the control group. Conclusion: A continuous 3 times 20 days of normal diet can simulate the disease characteristics of human non-alcoholic steatohepatitis in a zebrafish.