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SREBP-2, a New Target of Metformin?

SREBP-2, a New Target of Metformin?

Fengxia Zhang, Wenxiu Sun, Jianbo Chen, Lusheng Jiang, Ping Yang, Yufang Huang, Aihua Gong, Shudong Liu, Shizhan Ma

Drug Des Devel Ther. 2018 Dec 6;12:4163-4170.

PMID: 30584280

Abstract:

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.
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.
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1985462	Metformin Related Compound C		1985-46-2	Price

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