Abstract: OBJECTIVE:To explore the roles of miR-34a and its downstream genes plus iron overload in rats with nonalcoholic fatty liver disease. METHODS:Thirty-six male SD rats of 5 weeks old were randomly divided into control diet group (basal diet),high iron diet group (basal diet containing 1% FeSO₄),high fat diet group (high fat diet 35% energy supply from fat) and high fat plus high iron diet group (high fat diet containing 1% FeSO₄). These rats were sacrificed after 12 weeks. Body weights were measured and liver lipid accumulation was observed by oil red O staining. The contents of ALT and AST in rat serum were detected. Quantitative real-time PCR (qPCR) was used to detect mRNA levels of miR-34a, silent information regulator (SIRT1) and peroxisome proliferator-activated receptor α (PPARα). SIRT1 and PPARα protein levels were detected by Western blot. RESULTS:Compared with control diet group,the body weight,the serum ALT level and the level of miR-34a in high fat diet group and high fat plus high iron diet group were increased significantly (P < 0.05). The levels of mRNA and protein expression of SIRT1 and its downstream PPARα were decreased (P < 0.05). The degree of lipid accumulation in the liver was gradually aggravated. Compared with high fat diet group,the levels of mRNA and protein expression of SIRT1 and PPARα in high fat plus high iron diet group were decreased significantly (P < 0.05). CONCLUSION:The combined effect of high fat and high iron diets could activate the expression of miR-34a and then inhibit the expression of downstream genes, thus aggravating liver lipid disorder in NAFLD rats.

Key words: nonalcoholic fatty liver disease, iron overload, miR-34a, lipid metabolism