scholarly journals Punicalagin and Punicalin Suppress the Adipocyte Differentiation through the Transcription Factors

2021 ◽  
Vol 17 (2) ◽  
pp. 157-167
Author(s):  
M Berkoz
2021 ◽  
Vol 11 (4) ◽  
pp. 1725
Author(s):  
Hee-Do Hong ◽  
Sun-Il Choi ◽  
Ok-Hwan Lee ◽  
Young-Cheul Kim

Although ginsenosides Rb1 and Rg3 have been identified as the significant ginsenosides found in red ginseng that confer anti-diabetic actions, it is unclear whether insulin-sensitizing effects are mediated by the individual compounds or by their combination. To determine the effect of ginsenosides Rb1 and Rg3 on adipocyte differentiation, 3T3-L1 preadipocytes were induced to differentiate the standard hormonal inducers in the absence or presence of ginsenosides Rb1 or Rg3. Additionally, we determined the effects of Rb1, Rg3, or their combination on the expression of genes related to adipocyte differentiation, adipogenic transcription factors, and the insulin signaling pathway in 3T3-L1 cells using semi-quantitative RT-PCR. Rb1 significantly increased the expression of CEBPα, PPARγ, and aP2 mRNAs. However, Rg3 exerted its maximal stimulatory effect on these genes at 1 μM concentration, while a high concentration (50 μM) showed inhibitory effects. Similarly, treatment with Rb1 and Rg3 (1 μM) increased the expression of IRS-1, Akt, PI3K, GLUT4, and adiponectin. Importantly, co-treatment of Rb1 and Rg3 (9:1) induced the maximal expression levels of these mRNAs. Our data indicate that the anti-diabetic activity of red ginseng is, in part, mediated by synergistic actions of Rb1 and Rg3, further supporting the significance of minor Rg3.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jieyun Hong ◽  
Shijun Li ◽  
Xiaoyu Wang ◽  
Chugang Mei ◽  
Linsen Zan

Sirtuins, NAD+-dependent deacylases and ADP-ribosyltransferases, are critical regulators of metabolism involved in many biological processes, and are involved in mediating adaptive responses to the cellular environment. SIRT4 is a mitochondrial sirtuin and has been shown to play a critical role in maintaining insulin secretion and glucose homeostasis. As a regulator of lipid homeostasis, SIRT4 can repress fatty acid oxidation and promote lipid anabolism in nutrient-replete conditions. Using real-time quantitative PCR (qPCR) to explore the molecular mechanisms of transcriptional regulation of bovine SIRT4 during adipocyte differentiation, we found that bovine SIRT4 is expressed at high levels in bovine subcutaneous adipose tissue. SIRT4 knockdown led to decreased expression of adipogenic differentiation marker genes during adipocyte differentiation. The core promoter of bovine SIRT4 was identified in the −402/−60 bp region of the cloned 2-kb fragment containing the 5′-regulatory region. Binding sites were identified in this region for E2F transcription factor-1 (E2F1), CCAAT/enhancer-binding protein β (CEBPβ), homeobox A5 (HOXA5), interferon regulatory factor 4 (IRF4), paired box 4 (PAX4), and cAMP responsive element-binding protein 1 (CREB1) by using Electrophoretic mobility shift assay (EMSA) and luciferase reporter gene assay. We also found that E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors (TFs) to regulate the differentiation of bovine adipocytes. In conclusion, our results shed light on the mechanisms underlying the transcriptional regulation of SIRT4 expression in bovine adipocytes.


1992 ◽  
Vol 12 (10) ◽  
pp. 4622-4633 ◽  
Author(s):  
S Enerbäck ◽  
B G Ohlsson ◽  
L Samuelsson ◽  
G Bjursell

When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipoprotein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements important for gradual activation of the LPL gene during adipocyte development in vitro. These elements, LP-alpha (-702 to -666) and LP-beta (-468 to -430), contain a striking similarity to a consensus sequence known to bind the transcription factors HNF-3 and fork head. Results of gel mobility shift assays and DNase I and exonuclease III in vitro protection assays indicate that factors with DNA-binding properties similar to those of the HNF-3/fork head family of transcription factors are present in adipocytes and interact with LP-alpha and LP-beta. We also demonstrate that LP-alpha and LP-beta were both capable of conferring a differentiation-linked expression pattern to a heterolog promoter, thus mimicking the expression of the endogenous LPL gene during adipocyte differentiation. These findings indicate that interactions with LP-alpha and LP-beta could be a part of a differentiation switch governing induction of the LPL gene during adipocyte differentiation.


2002 ◽  
Vol 361 (3) ◽  
pp. 629-633 ◽  
Author(s):  
Makoto NISHIZUKA ◽  
Tomoko TSUCHIYA ◽  
Tsutomu NISHIHARA ◽  
Masayoshi IMAGAWA

Using a subtraction method, we have isolated genes that are induced early in the differentiation of mouse 3T3-L1 preadipocyte cells into adipocytes. These include the genes encoding transcription factors and signalling proteins, as well as unknown genes. Bach1, a transcription factor, and ARA70, a cofactor, were rapidly induced during differentiation. The induction of these two genes was observed only in growth-arrested 3T3-L1 cells, and not in proliferating cells. In NIH-3T3 cells, no induction was observed under either set of conditions. These results strongly indicate that Bach1 and ARA70 have valuable roles at the onset of adipocyte differentiation.


2021 ◽  
Author(s):  
Azam Armanmehr ◽  
Hossein Jafari Khamirani ◽  
Sina Zoghi ◽  
Mehdi Dianatpour

Background: Metabolic syndrome (MetS) is a group of signs and symptoms that are associated with a higher risk of Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Diseases (CVDs). The major risk factor for developing MetS is abdominal obesity that is caused by an increase in adipocyte size or number. Adipocyte number multiplication is caused by the differentiation of mesenchymal stem cells into adipose tissue. Numerous studies have evaluated the expression of key transcription factors including PPARG and CEBPB during adipocyte differentiation in murine cells such as 3T3-L1 cell line. In order to comprehend the expression changes during the process of fat accumulation in adipose tissue derived stem cells (ASCs), we compared the expression of DYRK1B, PPARG, and CEBPB in undifferentiated and differentiated ASCs into mature adipocytes between the patient (harboring DYRK1b R102C) and control (healthy individuals) groups. Methods: Gene expression was evaluated on eighth days pre-induction and days 1, 5, and 15 post-induction. The pluripotent capacity of ASCs and the potential for differentiation into adipocytes were confirmed by flow cytometry analysis of surface markers (CD34, CD44, CD105, and CD90), and Oil red O staining, respectively. Expressions of DYRK1B, PPARG, and CEBPB were assessed by RT-PCR in patients' and normal individuals' samples. Results: The expression of DYRK1B kinase and transcription factors (CEBPB and PPARG) are significantly higher in adipose derived stem cells harboring DYRK1b R102C compared to non-carriers on days 5 and 15 during adipocyte differentiation. These proteins may be suitable targets for therapeutic strategies in obesity and obesity related disorders like metabolic syndrome. Furthermore, AZ191 exhibited a potent and selective inhibitory activity toward DYRK1B and CEBPB. Conclusion: CEBPB, PPARA, and DYRK1B contribute to adipogenesis and the development of metabolic syndrome; thus, they can be harnessed in developing therapeutic agents against metabolic syndrome.


2020 ◽  
Vol 21 (9) ◽  
pp. 3383
Author(s):  
Kyung-Eun Lee ◽  
Youn-Hwa Nho ◽  
Seok Kyun Yun ◽  
Sung-Min Park ◽  
Seunghyun Kang ◽  
...  

In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid components of caviar extract, induces intracellular lipid accumulation and the expression of adiponectin in adipocytes. Although adipocytes are well known to be associated with the skin dermis by secreting various factors (e.g., adiponectin), the effects of caviar extract and DHA on the skin are not well studied. Here, we demonstrate the effects of caviar extract and DHA on adipocyte differentiation and adiponectin production, resulting in a preventive role in UV-irradiated skin aging. Caviar extract and DHA enhanced adipocyte differentiation and promoted the synthesis of transcription factors controlling adipocyte differentiation and adiponectin. In addition, the mRNA expression levels of matrix metalloproteinase-1 (MMP-1) were decreased in UVB-irradiated Hs68 fibroblasts that were cultured in conditioned medium from caviar extract or DHA-treated differentiated adipocytes. Taken together, these results indicate that caviar extract and DHA induce adipocyte differentiation and adiponectin production, thereby inhibiting UVB-induced premature skin aging via the suppression of MMP-1 production.


2019 ◽  
Vol 53 (3) ◽  
pp. 438-441
Author(s):  
A. Greco ◽  
D. V. Vaipan ◽  
V. A. Tkachuk ◽  
D. N. Penkov

2010 ◽  
Vol 30 (14) ◽  
pp. 3412-3420 ◽  
Author(s):  
C. F. Zizola ◽  
S. K. Frey ◽  
S. Jitngarmkusol ◽  
B. Kadereit ◽  
N. Yan ◽  
...  

ABSTRACT Adipogenesis is governed by a well-documented cascade of transcription factors. However, less is known about non-transcription factors that govern early stages of adipogenesis. Here we show that cellular retinol-binding protein type I (CRBP-I), a small cytosolic binding protein for retinol and retinaldehyde, is specifically restricted to preadipocytes in white adipose tissue. The absence of CRBP-I in mice (CRBP-I-KO mice) leads to increased adiposity. Despite increased adiposity, CRBP-I-KO mice remain more glucose tolerant and insulin sensitive during high-fat-diet feeding. 3T3-L1 cells deficient in CRBP-I or mouse embryonic fibroblasts derived from CRBP-I-KO mice had increased adipocyte differentiation and triglyceride (TG) accumulation. This was due to increased expression and activity of PPARγ, while other transcription factor pathways in early and late differentiation remained unchanged. Conversely, the overexpression of CRBP-I in 3T3-L1 cells results in decreased TG accumulation. In conclusion, CRBP-I is a cytosolic protein specifically expressed in preadipocytes that regulates adipocyte differentiation in part by affecting PPARγ activity.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Dong Hoon Kwak ◽  
Ji-Hye Lee ◽  
Dong-Gun Kim ◽  
Taesoo Kim ◽  
Kwang Jin Lee ◽  
...  

Hwangryunhaedok-tang (HRT) has been long used as traditional medicine in Asia. However, inhibitory role of HRT is unclear in early stage of 3T3-L1 adipocyte differentiation related to signaling. In the present study, we investigated the inhibitory effects of HRT on upstream signaling of peroxisome proliferation-activity receptor-γ(PPAR-γ) and CCAAT/enhancer binding protein-β(C/EBP-β) expression in differentiation of 3T3-L1 preadipocytes. We found that HRT significantly inhibited the adipocyte differentiation by downregulating several adipocyte-specific transcription factors including PPAR-γ, C/EBP-α, and C/EBP-βin 3T3-L1 preadipocytes. Furthermore, we observed that HRT markedly inhibited the differentiation media-mediated phosphorylation of Raf/extracellular mitogen-activated protein kinase 1 (MEK1)/signal-regulated protein kinase 1/2 (ERK1/2) and phosphorylation of phosphoinositide-dependent kinase 1 (PDK1)/Akt. These results indicate that anti-adipogenesis mechanism involves the downregulation of the major transcription factors of adipogenesis including PPAR-γand C/EBP-αthrough inhibition of Raf/MEK1/ERK1/2 phosphorylation and PDK1/Akt phosphorylation by HRT. Furthermore, high performance liquid chromatography (HPLC) analysis showed HRT contains active antiobesity constituents such as palmatine, berberine, geniposide, baicalin, baicalein, and wogonin. Taken together, this study suggested that anti-adipogenesis effects of HRT were accounted by downregulation of Raf/MEK1/ERK1/2 pathway and PDK1/Akt pathway during 3T3-L1 adipocyte differentiation.


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