[Effect of JAZF1 over-expression on high-fat diet-induced non-alcoholic fatty liver disease]

Objective: To investigate the effects of juxtaposed with another zinc finger gene 1 (JAZF1) over-expression on the levels of pro-inflammatory cytokines in high-fat diet (HFD)-induced mouse fatty liver and its associated mechanisms. Methods: Twenty male C57BL/6J (3 weeks old) and 10 male JAZF1 transgenic (JAZF1-Tg) mice were randomly divided into three groups: wide-type with normal diet (NF group,n= 10), wide-type with high-fat diet (HF group,n= 10), and JAZF1-Tg with high-fat diet (HJ group,n= 10). All mice were fed with the corresponding diet for 12 weeks, and their food consumption and body weight were measured periodically. After 12 weeks, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), and alanine aminotransferase (ALT) in the blood and liver tissue from each group were measured. TG concentration in liver tissue was determined using an enzymatic assay, and the mRNA expression of tumor necrosis factor-α(TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) in the liver was measured by RT-PCR. In addition, the expression of p-JNK/JNK, p-p-38 MAPK/p-38 MAPK, p-ERK/ERK, IκBα, andβ-actin (reference) in the liver was determined using Western blot.. Results: (1) Body weight, FBG, INS, TC, and ALT were significantly reduced in the HJ group compared with those of the HF group (31.19±0.81 vs 36.07±1.43, 6.94±0.32 vs 8.14±0.36, 31.09±2.12 vs 45.21±3.34, 3.05±0.07 vs 3.81±0.08, 54.75±4.92 vs 68.09±5.15, respectively;P< 0.05). There were no significant differences in TG and FFA between the HJ and HF groups (0.72±0.05 vs 0.81±0.03, 0.81±0.4 vs 0.87±0.03; bothP> 0.05). (2) There was no significant difference in liver TG concentration between the HJ and HF groups (35.49±3.17 vs 38.26±3.59,P> 0.05). (3) Compared with the HF group, the HJ group had significantly reduced mRNA expression of TNF-α, MCP-1, and IL-8 (2.54TNF-αvs 8.64±0.73, 1.19±0.73,vs 3.93±0.18, 5.09±0.48 vs 9.09±0.89; allP< 0.01), significantly reduced protein expression of p-JNK and p-p-38 MAPK (0.92±0.06 vs 1.51±0.01, 1.07±0.04 vs 1.45±0.04; bothP< 0.01), and significantly increased protein expression of IκBα(0.99±0.06 vs 0.79±0.05,P< 0.01) in liver tissue. However, no significant difference was observed in the p-ERK level between the HJ and HF groups (P> 0.05). Conclusion: Upregulation of JAZF1 expression can significantly inhibit the expression of TNF-α, MCP-1, and IL-8 in the liver of mice on HFD. This attenuation may be closely associated with the reduced activation of the JNK, p-38 MAPK, and NF-κB pathways.