Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors
Obesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it poten...
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2021-11-01
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author | Jelena Jakab Milorad Zjalić Štefica Mikšić Ivan Tušek Vesna Ćosić Nikola Volarić Dario Nakić Aleksandar Včev Blaženka Miškić |
author_facet | Jelena Jakab Milorad Zjalić Štefica Mikšić Ivan Tušek Vesna Ćosić Nikola Volarić Dario Nakić Aleksandar Včev Blaženka Miškić |
author_sort | Jelena Jakab |
collection | DOAJ |
description | Obesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it potential target for the therapeutic approach to obesity. An increasing number of studies confirm the pleiotropic action of the combined treatment with metformin and statins, suggesting their anti-hypertensive, anti-inflammatory, and anti-adipogenic effect. The aim of this study was to analyze the effect of different doses of metformin (MET) and simvastatin (SIM) on the expression of key transcription factors of adipogenesis. Mouse 3T3-L1 preadipocytes were induced to differentiation in adipogenic medium with sustained MET and SIM treatment to assess the effect on adipogenesis. Nine days after initiating adipogenesis, the cells were prepared for further experiments, including Oil Red O staining, RT-PCR, Western blotting, and immunocytochemistry. Treating the cells with the combination of MET and SIM slightly reduced the intensity of Oil Red O staining compared with the control group, and down-regulated mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1C. In conclusion, the inhibitory effect of MET and SIM on adipocyte differentiation, as indicated by decreased lipid accumulation, appears to be mediated through the down-regulation of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding pro-tein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1C). |
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spelling | doaj.art-190eb287e88647dabd071c1f93ccfe0f2023-11-23T07:44:17ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-11-014332082209710.3390/cimb43030144Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription FactorsJelena Jakab0Milorad Zjalić1Štefica Mikšić2Ivan Tušek3Vesna Ćosić4Nikola Volarić5Dario Nakić6Aleksandar Včev7Blaženka Miškić8Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera, 4, 31000 Osijek, CroatiaFaculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera, 4, 31000 Osijek, CroatiaFaculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Crkvena 21, 31000 Osijek, CroatiaFaculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21137 Novi Sad, SerbiaFaculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Crkvena 21, 31000 Osijek, CroatiaFaculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera, 4, 31000 Osijek, CroatiaZadar General Hospital, Ul. Bože Peričića 5, 23000 Zadar, CroatiaFaculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Crkvena 21, 31000 Osijek, CroatiaFaculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Crkvena 21, 31000 Osijek, CroatiaObesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it potential target for the therapeutic approach to obesity. An increasing number of studies confirm the pleiotropic action of the combined treatment with metformin and statins, suggesting their anti-hypertensive, anti-inflammatory, and anti-adipogenic effect. The aim of this study was to analyze the effect of different doses of metformin (MET) and simvastatin (SIM) on the expression of key transcription factors of adipogenesis. Mouse 3T3-L1 preadipocytes were induced to differentiation in adipogenic medium with sustained MET and SIM treatment to assess the effect on adipogenesis. Nine days after initiating adipogenesis, the cells were prepared for further experiments, including Oil Red O staining, RT-PCR, Western blotting, and immunocytochemistry. Treating the cells with the combination of MET and SIM slightly reduced the intensity of Oil Red O staining compared with the control group, and down-regulated mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1C. In conclusion, the inhibitory effect of MET and SIM on adipocyte differentiation, as indicated by decreased lipid accumulation, appears to be mediated through the down-regulation of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding pro-tein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1C).https://www.mdpi.com/1467-3045/43/3/144adipocytesadipogenesisobesitymetforminsimvastatin |
spellingShingle | Jelena Jakab Milorad Zjalić Štefica Mikšić Ivan Tušek Vesna Ćosić Nikola Volarić Dario Nakić Aleksandar Včev Blaženka Miškić Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors Current Issues in Molecular Biology adipocytes adipogenesis obesity metformin simvastatin |
title | Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors |
title_full | Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors |
title_fullStr | Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors |
title_full_unstemmed | Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors |
title_short | Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors |
title_sort | effect of metformin and simvastatin in inhibiting proadipogenic transcription factors |
topic | adipocytes adipogenesis obesity metformin simvastatin |
url | https://www.mdpi.com/1467-3045/43/3/144 |
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