SREBP-2, a new target of metformin?
Authors Zhang F, Sun W, Chen J, Jiang L, Yang P, Huang Y, Gong A, Liu S, Ma S
Received 9 October 2018
Accepted for publication 21 November 2018
Published 6 December 2018 Volume 2018:12 Pages 4163—4170
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Fengxia Zhang,1,* Wenxiu Sun,2,* Jianbo Chen,3 Lusheng Jiang,3 Ping Yang,3 Yufang Huang,3 Aihua Gong,3 Shudong Liu,3 Shizhan Ma4
1Department of Neurology, Affiliated Hospital of Shandong Traditional Chinese Medicine University, Jinan 250011, China; 2Department of Pharmacy, Taishan Vocational College of Nursing, Taian 271000, China; 3Department of Endocrinology, Shandong Rongjun General Hospital, Jinan 250013, China; 4Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
*These authors contributed equally to this work
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.
Keywords: type 2 diabetes mellitus, cholesterol, metformin, AMP-activated protein kinase, sterol regulatory element-binding protein-2
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