Background
Metformin, as the first-line treatment anti-diabetic drug, represents increasing evidence of a potential efficacy in improving dyslipidemia. However, the exact molecular mechanism(s) by which metformin influences lipid metabolism remains incompletely understood.
Conclusion
Our preliminary results demonstrate that metformin as a first-line and initial medication suppresses the synthesis of SREBP-2 and upregulates LDLR, and consequently decreases cholesterol production via activation of AMPK, at least partly. These findings suggest a therapeutic target and potential beneficial effects of metformin on the prevention of dyslipidemia or related diseases.
Methods
The HepG2 cells were treated with metformin and the AMP-activated protein kinase (AMPK) inhibitor compound C or a dominant-negative form of AMPK plasmid. ELISA assay was employed to measure AMPK activity, and cellular cholesterol content was determined by enzymatic colorimetric method. RT-PCR and western blotting were used to detect SREBP-2 mRNA levels and its target protein levels.
Results
We found that metformin significantly stimulated AMPK activity and decreased intracellular total cholesterol contents in HepG2 cells. Metformin reduced the sterol regulatory element-binding protein-2 (SREBP-2) and its downstream target proteins and increased low-density lipoprotein receptor (LDLR) levels.