SREBP-2, a new target of metformin?
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 Colleg...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2018-12-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/srebp-2-a-new-target-of-metformin-peer-reviewed-article-DDDT |
| _version_ | 1819096717148028928 |
|---|---|
| author | Zhang F Sun W Chen J Jiang L Yang P Huang Y Gong A Liu S Ma S |
| author_facet | Zhang F Sun W Chen J Jiang L Yang P Huang Y Gong A Liu S Ma S |
| author_sort | Zhang F |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-22T00:03:38Z |
| format | Article |
| id | doaj.art-6d8456abcdd64be987edb6ce4c4a9434 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-22T00:03:38Z |
| publishDate | 2018-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-6d8456abcdd64be987edb6ce4c4a94342022-12-21T18:45:37ZengDove Medical PressDrug Design, Development and Therapy1177-88812018-12-01Volume 124163417042858SREBP-2, a new target of metformin?Zhang FSun WChen JJiang LYang PHuang YGong ALiu SMa SFengxia 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-2https://www.dovepress.com/srebp-2-a-new-target-of-metformin-peer-reviewed-article-DDDTType 2 diabetes mellitusCholesterolMetforminAMP-activated protein kinaseSterol regulatory element-binding protein-2 |
| spellingShingle | Zhang F Sun W Chen J Jiang L Yang P Huang Y Gong A Liu S Ma S SREBP-2, a new target of metformin? Drug Design, Development and Therapy Type 2 diabetes mellitus Cholesterol Metformin AMP-activated protein kinase Sterol regulatory element-binding protein-2 |
| title | SREBP-2, a new target of metformin? |
| title_full | SREBP-2, a new target of metformin? |
| title_fullStr | SREBP-2, a new target of metformin? |
| title_full_unstemmed | SREBP-2, a new target of metformin? |
| title_short | SREBP-2, a new target of metformin? |
| title_sort | srebp 2 a new target of metformin |
| topic | Type 2 diabetes mellitus Cholesterol Metformin AMP-activated protein kinase Sterol regulatory element-binding protein-2 |
| url | https://www.dovepress.com/srebp-2-a-new-target-of-metformin-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT zhangf srebp2anewtargetofmetformin AT sunw srebp2anewtargetofmetformin AT chenj srebp2anewtargetofmetformin AT jiangl srebp2anewtargetofmetformin AT yangp srebp2anewtargetofmetformin AT huangy srebp2anewtargetofmetformin AT gonga srebp2anewtargetofmetformin AT lius srebp2anewtargetofmetformin AT mas srebp2anewtargetofmetformin |