జర్నల్ ఆఫ్ మెటబాలిక్ సిండ్రోమ్

The Changes of the Expression of PGC-1α and the Level of Oxidative Stress in NAFLD as well as the Effects of Metformin on NAFLD

Abstract

Jian-hua Jiang, Jing Cheng, Bao Zhang, Shi-xia Guan and Li-li Hou

Purpose: The objective of this study was to determine how metformin regulates the major activator of hepatic gluconeogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and the PGC-1α controlled liver functions.

Methods: In population study, we selected 40-69 years old patients with NAFLD, 77, and 102 healthy subjects as a control group. We detect the levels of serum PGC-1α, MDA and the activity of SOD of the two groups. In vitro study, L-02 cells were treated by 20 μg/ml oleic acid to induce the NAFLD cells model. The control group added ordinary 1640 culture medium. The model group cells were cultured in the medium containing 2.5, 5, 7.5mmol/l concentrations of metformin. Used RT-PCR analysis of PGC-1α mRNA, detected the level of triglycerides in cells, measured the content of MDA and the activity of SOD.

Results: In population study, the level of MDA in the case group were increased obviously and the activity of SOD was decreased compared with the control group. There had no difference of the level of PGC-1α between the two groups. In vitro study, compared with the control groups, the level of triglyceride and the concentration of MDA in the model groups were increased and the activity of SOD as well as the expression of PGC-1α mRNA were decreased; When the final concentration of metformin is 7.5 mmol/l, the level of triglyceride and MDA were decreased as well as the activity of SOD and the expression of PGC-1α mRNA were increased compared with the model group.

Conclusion: Metformin can adjust the expression of PGC-1α and the level of oxidative stress which can decrease the fat accumulation, Our results thus identify selective modulation of hepatic PGC-1α functions as a novel mechanism involved in the therapeutic action of metformin.