Acta Academiae Medicinae Sinica

Abstract:

Objective To investigate the roles of microRNA-21 (miR-21) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) with high-fat diet-induced insulin resistance (IR) and diabetes mellitus (DM) mice model. Methods Eight-week-old C57BL/6 mice were allocated into control group,IR group,and DM group. Body mass was recorded. Intraperitoneal glucose tolerance test was performed to determine any abnormal glucose metabolism. The liver pathological changes were detected by biopsy. Changes in free blood glucose,free serum insulin,blood fat and tumor necrosis factor α level were measured. Differences in miR-21 expression and peroxidase proliferator-activated receptor subtypes (PPAR-γ and PPAR-α) and adipocyte fatty acid binding protein (aP2) in the liver were detected both at the mRNA and protein levels. Results After one 8-week high-fat diet,the body mass,free serum insulin,and homeostasis model IR index significantly increased in the IR group (P<0.01,P<0.05,compared with control group),while the free blood glucose increased and the free serum insulin decreased in DM group(P<0.05). Free serum insulin level were significantly increased in IR group (P<0.05). Serum tumor necrosis factor-α levels exhibited an upward trend in control group,IR group,and DM group (P<0.05,P<0.01). With exacerbation in NAFLD,liver miR-21 expression level went further down in both IR and DM groups (P<0.05). The downregulated miR-21 expression level showed negative correlation with upregulated PPAR-α,αP2,and PPAR-γ genetic expression (r=-0.696,r=-0.664,and r=-0.766,respectively;P<0.05) in IR group and with upregulated PPAR-α and PPAR-γ genetic expression in DM group (r=-0.676 and r=-0.550,respectively;P<0.05). In terms of the changes in protein expression level,only on the protein expressions of aP2 and PPAR-γ in IR group showed significant change (P<0.05,P<0.01,compared with control group). Conclusions The miR-21 expression is downregulated in both IR and DM-induced NAFLD mice. It may be involved in the pathogenesis of NAFLD by regulating the expressions of PPAR subtypes.

Key words: non-alcoholic fatty liver disease, microRNA-21, insulin resistance, diabetes mellitus, peroxisome proliferator-activated receptor subtypes