scholarly journals Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 288
Author(s):  
Tomohiro Ibata ◽  
Jingya Lyu ◽  
Hitomi Imachi ◽  
Kensaku Fukunaga ◽  
Seisuke Sato ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Lipid Content ◽  
Hepg2 Cells ◽  
Promoter Region ◽  
Promoter Activity ◽  
Pi3k Pathway ◽  
Dominant Negative ◽  
Nuclear Accumulation ◽  
Hepatic Lipid ◽  
Abca1 Expression

ATP-binding cassette transporter A1 (ABCA1) is a key regulator of lipid efflux, and the absence of ABCA1 induces hepatic lipid accumulation, which is one of the major causes of fatty liver. 2-Methoxyestradiol (2-ME2) has been demonstrated to protect against fatty liver. In this study, we investigated the effects of 2-ME2 on the hepatic lipid content and ABCA1 expression. We found that 2-ME2 dose-dependently increased ABCA1 expression, and therefore, the lipid content was significantly decreased in HepG2 cells. 2-ME2 enhanced the ABCA1 promoter activity; however, this effect was reduced after the inhibition of the PI3K pathway. The overexpression of Akt or p110 induced ABCA1 promoter activity, while dominant-negative Akt diminished the ability of 2-ME2 on ABCA1 promoter activity. Further, 2-ME2 stimulated the rapid phosphorylation of Akt and FoxO1 and reduced the nuclear accumulation of FoxO1. Chromatin immunoprecipitation confirmed that FoxO1 bonded to the ABCA1 promoter region. The binding was reduced by 2-ME2, which facilitated ABCA1 gene transcription. Furthermore, mutating FoxO1-binding sites in the ABCA1 promoter region or treatment with FoxO1-specific siRNA disrupted the effect of 2-ME2 on ABCA1 expression. All of our results demonstrated that 2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes.

scholarly journals The NRF-1/α-PAL transcription factor regulates human E2F6 promoter activity

2004 ◽  
Vol 383 (3) ◽  
pp. 529-536 ◽  
Author(s):  
Zoulika KHERROUCHE ◽  
Yvan DE LAUNOIT ◽  
Didier MONTE
Keyword(s):  
Promoter Region ◽  
Promoter Activity ◽  
Core Promoter ◽  
Dominant Negative ◽  
Site Directed Mutagenesis ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Dnase I Footprinting ◽  
Dominant Negative Form

E2F6 is widely expressed in human tissues and cell lines. Recent studies have demonstrated its involvement in developmental patterning and in the regulation of various genes implicated in chromatin remodelling. Despite a growing number of studies, nothing is really known concerning the E2F6 expression regulation. To understand how cells control E2F6 expression, we analysed the activity of the previously cloned promoter region of the human E2F6 gene. DNase I footprinting, gel electrophoreticmobility shift, transient transfection and site-directed mutagenesis experiments allowed the identification of two functional NRF-1/α-PAL (nuclear respiratory factor-1/α-palindrome-binding protein)-binding sites within the human E2F6 core promoter region, which are conserved in the mouse and rat E2F6 promoter region. Moreover, ChIP (chromatin immunoprecipitation) analysis demonstrated that overexpressed NRF-1/α-PAL is associated in vivo with the E2F6 promoter. Furthermore, overexpression of full-length NRF-1/α-PAL enhanced E2F6 promoter activity, whereas expression of its dominant-negative form reduced the promoter activity. Our results indicate that NRF-1/α-PAL is implicated in the regulation of basal E2F6 gene expression.

1906-P: Effects of a Carbohydrate-Restricted Diet on Hepatic Lipid Content in Adolescents with Nonalcoholic Fatty Liver Disease

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1906-P
Author(s):  
AMY M. GOSS ◽  
SHIMA DOWLA ◽  
AMBIKA P. ASHRAF ◽  
MARK BOLDING ◽  
SHANNON A. MORRISON ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Content ◽  
Fatty Liver Disease ◽  
Restricted Diet ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Content

scholarly journals Adiponectin Upregulates SHBG Production: Molecular Mechanisms and Potential Implications

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2820-2830 ◽  
Author(s):  
Rafael Simó ◽  
Cristina Saez-Lopez ◽  
Albert Lecube ◽  
Cristina Hernandez ◽  
Jose Manuel Fort ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Content ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Acid Oxidation ◽  
Hepatic Lipid ◽  
Human Liver Biopsies ◽  
Liver Biopsies ◽  
Hepatic Lipid Content

Epidemiological studies have shown that plasma SHBG levels correlate with plasma adiponectin levels, both in men and women. There are no reports describing any molecular mechanism by which adiponectin regulates hepatic SHBG production. The aim of the present study is to explore whether adiponectin regulates SHBG production by increasing HNF-4α levels through reducing hepatic lipid content. For this purpose, in vitro studies using human HepG2 cells, as well as human liver biopsies, were performed. Our results show that adiponectin treatment increased SHBG production via AMPK activation in HepG2 cells. Adiponectin treatment decreased the mRNA and protein levels of enzymes related to hepatic lipogenesis (ACC) and increased those related to fatty acid oxidation (ACOX and CPTI). These adiponectin-induced changes in hepatic enzymes resulted in a reduction of total TG and FFA and an increase of HNF-4α. When HNF-4α expression was silenced by using siRNA, adiponectin-induced SHBG overexpression was blocked. Furthermore, adiponectin-induced upregulation of SHBG production via HNF-4α overexpression was abrogated by the inhibition of fatty acid oxidation or by the induction of lipogenesis with a 30mM glucose treatment in HepG2 cells. Finally, adiponectin levels correlated positively and significantly with both HNF-4α and SHBG mRNA levels in human liver biopsies. Our results suggest for the first time that adiponectin increases SHBG production by activating AMPK, which reduces hepatic lipid content and increases HNF-4α levels.

scholarly journals Functional characterization of the human phosphodiesterase 7A1 promoter

2003 ◽  
Vol 373 (3) ◽  
pp. 835-843 ◽  
Author(s):  
Mònica TORRAS-LLORT ◽  
Fernando AZORÍN
Keyword(s):  
T Cells ◽  
Promoter Region ◽  
Promoter Activity ◽  
Cpg Island ◽  
Functional Characterization ◽  
Regulatory Elements ◽  
Dominant Negative ◽  
Nuclear Factor ◽  
Jurkat T Cells

In this paper, the human phosphodiesterase 7A1 (hPDE7A1) promoter region was identified and functionally characterized. Transient transfection experiments indicated that a 2.9 kb fragment of the hPDE7A1 5′-flanking region, to position −2907, has strong promoter activity in Jurkat T-cells. Deletion analysis showed that the proximal region, up to position −988, contains major cis-regulatory elements of the hPDE7A1 promoter. This minimal promoter region contains a regulatory CpG island which is essential for promoter activity. The CpG island contains three potential cAMP-response-element-binding protein (CREB)-binding sites that, as judged by in vivo dimethyl sulphate (DMS) footprinting, are occupied in Jurkat T-cells. Moreover, over-expression of CREB results in increased promoter activity, but, on the other hand, promoter activity decreases when a dominant-negative form of CREB (KCREB) is over-expressed. In vivo DMS footprinting strongly indicates that other transcription factors, such Ets-2, nuclear factor of activated T-cells 1 (NFAT-1) and nuclear factor κB (NF-κB), might also contribute to the regulation of hPDE7A1 promoter. Finally, hPDE7A1 promoter was found to be induced by treatment with PMA, but not by treatment with dibutyryl cAMP or forskolin. These results provide insights into the factors and mechanisms that regulate expression of the hPDE7A gene.

scholarly journals OR06-05 Inadequate High Mitochondrial ATP-Synthesis Explains “Non-Fatty-Liver” in Patients with Acromegaly

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Paul Fellinger ◽  
Peter Wolf ◽  
Lorenz Pfleger ◽  
Krssak Martin ◽  
Klavins Kristaps ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Liver ◽  
Lipid Content ◽  
Atp Synthesis ◽  
Synthesis Rate ◽  
Mitochondrial Activity ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Active Acromegaly

Abstract Background Patients with active acromegaly exhibit low hepatocellular lipid content (HCL) despite pronounced insulin resistance. This contrasts the strong association of insulin resistance with non-alcoholic fatty liver disease in the general population. Acromegaly may therefore help to elucidate antisteatotic pathways. Since low HCL in acromegaly might be caused by changes in oxidative substrate metabolism and interorgan crosstalk we investigated mitochondrial activity and plasma metabolomics as well as lipidomics in active acromegaly. Approach & Results Patients In this cross-sectional study, 15 patients with active acromegaly (ACRO) and 17 healthy controls (CON) matched for age, BMI, gender and body composition were included. All participants were invited to undergo 31P/1H-7T-MR-spectroscopy of the liver and skeletal muscle, as well as plasma metabolomic profiling and an oral glucose tolerance test. In comparison to CON, ACRO were insulin resistant, and showed significant lower HCL but their hepatic ATP-synthesis rate adjusted to HCL was significantly increased (h_kATP:0.19[0.14;0.24]vs0.28[0.22;0.34]s-1);p=0.024). Furthermore, the HCL-adjusted ratio of unsaturated to saturated intracellular fatty acids was decreased in ACRO (8.4%vs25.5% of HCL,p<0.04). In skeletal muscle, intramyocellular lipids and ATP-synthesis rate were significantly decreased in ACRO. Plasma lipids and lipidomics did not differ between ACRO and CON, but decreased levels of carnitine species were observed in ACRO. Conclusions The dissociation of hepatic lipid content and peripheral insulin resistance in acromegaly is associated with high mitochondrial activity as indicated by liver specific upregulation of the ATP-synthesis rate. This is paralleled by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a change in circulating carnitine species, also reflecting an increased mitochondrial activity. Our findings hint at potential direct effects of growth hormone excess on hepatic lipid and energy metabolism.

scholarly journals Apigenin Alleviates Non-Alcoholic Fatty Liver Disease by Downregulating the NLRP3/NF-κB Signaling Pathway in Mice

2021 ◽  
Author(s):  
Zheng Lu ◽  
Lu Liu ◽  
Shunxin Zhao ◽  
Jiangtao Zhao ◽  
Sujun Li
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract Background: Apigenin, a flavone found in several plant foods with various biological properties including anti-inflammatory and other abilities, alleviated non-alcohol fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the mechanisms underlying this protection of inflammation and NAFLD has not been known clearly. Methods: Low density lipoprotein receptor-deficient (Ldlr-/-) mice were fed with HFD diet to induce NAFLD model and were treated with apigenin (50 mg/kg/day) for eight weeks. Hepatic lipid accumulation and inflammation in the livers were analyzed and quantified. In vitro experiments, HepG2 cells were stimulated by LPS plus oleic acid (OA) in the absence of presence of apigenin (50μM). Lipid accumulation and the effect of apigenin on NLRP3/NF-κB signaling pathway was investigated.Results: Apigenin administration reduce the weight, plasma lipid levels in Ldlr-/- mice when fed an HFD. Apigenin (50 mg/kg/day) treated mice displayed reduced hepatic lipid accumulation and inflammation in the livers of mice given the HFD diet. Treating the HepG2 cells with apigenin reduced lipid accumulation. And, apigenin also inhibited activation of NLRP3/NF-κB signaling pathway stimulated by OA together with LPS. Conclusions: Our results indicated that apigenin supplementation prevented NAFLD via down-regulating the NLRP3/NF-κB signaling pathway in mice, and suggested apigenin might be a potential therapeutic agent for the prevention of NAFLD.

PCSK9 REDUCES HEPATIC LIPID CONTENT AND CONFERS PROTECTION AGAINST ER STRESS AND ROS IN HEPG2 CELLS

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Jae Hyun Byun ◽  
Paul Lebeau ◽  
Ali Al‐Hashimi ◽  
Khrystyna C. Platko ◽  
Bernardo Trigatti ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Content ◽  
Hepg2 Cells ◽  
Hepatic Lipid ◽  
Hepatic Lipid Content

scholarly journals Expression of taurine transporter is regulated through the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway and contributes to cytoprotection in HepG2 cells

2004 ◽  
Vol 382 (1) ◽  
pp. 177-182 ◽  
Author(s):  
Takashi ITO ◽  
Yasushi FUJIO ◽  
Mayo HIRATA ◽  
Tomoka TAKATANI ◽  
Takahisa MATSUDA ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Hepg2 Cells ◽  
Promoter Activity ◽  
Binding Protein ◽  
Dominant Negative ◽  
Taurine Transporter ◽  
Hypertonic Medium ◽  
Hypertonic Stress ◽  
Gene Assay ◽  
Responsive Element

In hypertonic environment, taurine accumulates in cells via activation of TauT (taurine transporter) as an adaptive regulation. Recent studies revealed that TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway regulated the expression of various molecules which protect cells against hypertonic stress. In the present study, we investigated the osmoregulatory mechanisms of TauT expression. TauT was up-regulated at both functional and transcriptional levels in HepG2 under hypertonic condition. The TonE site was identified in the promoter region of TauT gene. Reporter gene assay revealed that promoter activity was increased under hypertonic conditions, whereas deletion or mutation of TonE sequence abolished the induction of the promoter activity in response to hypertonicity. By using the reporter gene plasmids containing a TonE site of TauT promoter (p2xTonE-Luc), it was demonstrated that a TonE site was sufficient for the hypertonicity-mediated activation of TauT promoter. Importantly, co-transfection of TauT promoter gene plasmid with wild-type TonEBP expression vector enhanced promoter activity under isotonic conditions, whereas dominant-negative TonEBP abrogated the TauT promoter activity induced by hypertonicity. Finally, treatment with taurine prevented HepG2 cells from cell death induced by hypertonic medium. These findings suggested that induction of TauT by hypertonicity is mediated by the activation of the TonE/TonEBP pathway and confers resistance to hypertonic stress.

Sign in / Sign up

Export Citation Format

Share Document