scholarly journals Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors

2021 ◽  
Vol 43 (3) ◽  
pp. 2082-2097
Author(s):  
Jelena Jakab ◽  
Milorad Zjalić ◽  
Štefica Mikšić ◽  
Ivan Tušek ◽  
Vesna Ćosić ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Element ◽  
Combined Treatment ◽  
Inhibitory Effect ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Oil Red O Staining ◽  
Oil Red O

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).

scholarly journals Nonylphenol Promotes the Differentiation of 3T3-L1 Preadipocytes

2021 ◽  
Author(s):  
lan Tang ◽  
Jie Xu ◽  
Jie Yu ◽  
Mei Wen Li
Keyword(s):  
Late Stage ◽  
Lipid Droplets ◽  
Binding Protein ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Induced Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein

Abstract BackgroundNonylphenol (NP) induces obesity, we elucidated the influence of NP on the differentiation of 3T3-L1 preadipocytes and characterize the key stages in the underlying mechanism.Methods3T3-L1 preadipocytes were cultured until contact inhibition occurred and subsequently induced to differentiate using the MDI (methylisobutylxanthine, dexamethasone, and insulin) induction protocol. The cells were exposed to NP during the middle and late stages of the MDI-induced differentiation. After 24 h of exposure to NP, cell growth and differentiation were evaluated under an inverted phase-contrast microscope, lipid deposition was assessed by Oil Red O (ORO) staining, and the levels of the lipid-metabolism–related proteins CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthesis (FAS), peroxisome proliferator-activated receptor γ (PPARγ), and sterol regulatory element binding protein 1 (SREBP1) were determined by western blotting.Results1) Compared with the control group, the lipid droplets in the NP-treated cells were significantly more abundant and bigger,and the levels of C/EBPα, FAS, PPARγ and SREBP1 were significantly higher (P < .001). 2) The intensity of ORO staining was stronger and there were more intensely stained lipid droplets in the NP-treated cells during the middle stages than the late stage，the levels of the C/EBPα, FAS, PPARγ and SREBP1 during the middle stages were approximately higher than those during the late stage (P < .001). ConclusionNP promotes proliferation, differentiation, and lipid accumulation in 3T3-L1 preadipocytes, and increases the expression of the C/EBPα, FAS, PPARγ and SREBP1，and NP mainly promotes the proliferation and differentiation of 3T3-L1 preadipocytes during the middle stages of the MDI-induced differentiation.

scholarly journals Regulation of Peroxisome Proliferator-Activated Receptor γ Expression by Adipocyte Differentiation and Determination Factor 1/Sterol Regulatory Element Binding Protein 1: Implications for Adipocyte Differentiation and Metabolism

1999 ◽  
Vol 19 (8) ◽  
pp. 5495-5503 ◽  
Author(s):  
Lluis Fajas ◽  
Kristina Schoonjans ◽  
Laurent Gelman ◽  
Jae B. Kim ◽  
Jamila Najib ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Pparγ Expression

ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor implicated in adipocyte differentiation and insulin sensitivity. We investigated whether PPARγ expression is dependent on the activity of adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1 (ADD-1/SREBP-1), another transcription factor associated with both adipocyte differentiation and cholesterol homeostasis. Ectopic expression of ADD-1/SREBP-1 in 3T3-L1 and HepG2 cells induced endogenous PPARγ mRNA levels. The related transcription factor SREBP-2 likewise induced PPARγ expression. In addition, cholesterol depletion, a condition known to result in proteolytic activation of transcription factors of the SREBP family, induced PPARγ expression and improved PPRE-driven transcription. The effect of the SREBPs on PPARγ expression was mediated through the PPARγ1 and -3 promoters. Both promoters contain a consensus E-box motif that mediates the regulation of the PPARγ gene by ADD-1/SREBP-1 and SREBP-2. These results suggest that PPARγ expression can be controlled by the SREBP family of transcription factors and demonstrate new interactions between transcription factors that can regulate different pathways of lipid metabolism.

scholarly journals The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6074
Author(s):  
Maciej Danielewski ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
Tomasz Sozański
Keyword(s):  
Transcription Factors ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Functions ◽  
The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

scholarly journals Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

2019 ◽  
Vol 20 (5) ◽  
pp. 1153 ◽  
Author(s):  
Nunzia D’Onofrio ◽  
Gorizio Pieretti ◽  
Feliciano Ciccarelli ◽  
Antonio Gambardella ◽  
Nicola Passariello ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Abdominal Fat ◽  
Control Group ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metformin Therapy ◽  
Ppar Γ ◽  
Visceral Abdominal Fat ◽  
Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

scholarly journals Anti-adipogenic effect of mastoparan B analogue peptide on 3T3-L1 preadipocytes

2018 ◽  
Vol 13 (4) ◽  
pp. 333-339
Author(s):  
Ji Hye Kim ◽  
Mi Jeong Jo ◽  
Hye Jin Go ◽  
Nam Gyu Park ◽  
Gun Do Kim
Keyword(s):  
Glycogen Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cardiovascular Effects ◽  
Peroxisome Proliferator ◽  
Preadipocyte Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Gsk 3Β ◽  
Adipogenic Effect

Mastoparan B (MP-B), a cationic tetradecapeptide isolated from the venom of the Vespa basalis, exhibits cardiovascular effects, local edema and antibacterial activity. In this study, the anti-adipogenic effect of an MP-B analogue and its mechanism of action in 3T3-L1 preadipocytes were studied. The MP-B analogue (MP-B12) inhibited preadipocyte differentiation and decreased the expression of adipogenic transcription factors, including CCAAT/enhancer binding protein-alpha (C/EBPα), nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein-1 (SREBP-1). Moreover, MP-B12 regulated the phosphorylation of Akt and glycogen synthase kinase-3 beta (GSK-3β), both of which play a role in preadipocyte differentiation, in which insulin and certain growth factors stimulated adipogenesis. This study demonstrates that MP-B12 inhibits preadipocyte differentiation and the accumulation of lipid droplets in 3T3-L1 preadipocytes and could potentially be used to treat obesity.Video Clip of Methodology:4 min 11 sec   Full Screen   Alternate  

Anti-Obesity Effect of Blumea balsamifera Extract in 3T3-L1 Preadipocytes and Adipocytes

2009 ◽  
Vol 37 (05) ◽  
pp. 843-854 ◽  
Author(s):  
Hiroaki Kubota ◽  
Akiko Kojima-Yuasa ◽  
Risako Morii ◽  
Xuedan Huang ◽  
Toshio Norikura ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein C ◽  
Peroxisome Proliferator ◽  
Industrialized Countries ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Element Binding Protein ◽  
Significant Attenuation ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Antidiabetic Effects

Obesity, the leading metabolic disease in the world, is a serious health problem in industrialized countries. We investigated the anti-obesity effect of Blumea balsamifera extract on adipocyte differentiation of 3T3-L1 preadipocytes and anti-obesity effect of 3T3-L1 adipocytes. We found that treatment with an extract of Blumea balsamifera suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and adipocytes. Furthermore, Blumea balsamifera extract brought significant attenuation of expressions of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT element binding protein (C/EBPs) and leptin, however, induced up-regulation of adiponectin at the protein level in 3T3-L1 preadipocytes and adipocytes. These results suggest that Blumea balsamifera extract may block adipogenesis, at least in part, by decreasing key adipogenic transcription factors in 3T3-L1 preadipocytes and may have antiatherogenic, anti-inflammatory, and antidiabetic effects through up-regulation of adiponectin in 3T3-L1 adipocytes.

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