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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Main Authors: Jelena Jakab, Milorad Zjalić, Štefica Mikšić, Ivan Tušek, Vesna Ćosić, Nikola Volarić, Dario Nakić, Aleksandar Včev, Blaženka Miškić
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/43/3/144
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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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