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SREBP-2, a new target of metformin?
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287532/ https://www.ncbi.nlm.nih.gov/pubmed/30584280 http://dx.doi.org/10.2147/DDDT.S190094 |
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author | Zhang, Fengxia Sun, Wenxiu Chen, Jianbo Jiang, Lusheng Yang, Ping Huang, Yufang Gong, Aihua Liu, Shudong Ma, Shizhan |
author_facet | Zhang, Fengxia Sun, Wenxiu Chen, Jianbo Jiang, Lusheng Yang, Ping Huang, Yufang Gong, Aihua Liu, Shudong Ma, Shizhan |
author_sort | Zhang, Fengxia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6287532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62875322018-12-24 SREBP-2, a new target of metformin? Zhang, Fengxia Sun, Wenxiu Chen, Jianbo Jiang, Lusheng Yang, Ping Huang, Yufang Gong, Aihua Liu, Shudong Ma, Shizhan Drug Des Devel Ther Original Research 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. Dove Medical Press 2018-12-06 /pmc/articles/PMC6287532/ /pubmed/30584280 http://dx.doi.org/10.2147/DDDT.S190094 Text en © 2018 Zhang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Zhang, Fengxia Sun, Wenxiu Chen, Jianbo Jiang, Lusheng Yang, Ping Huang, Yufang Gong, Aihua Liu, Shudong Ma, Shizhan SREBP-2, a new target of metformin? |
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 | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287532/ https://www.ncbi.nlm.nih.gov/pubmed/30584280 http://dx.doi.org/10.2147/DDDT.S190094 |
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