Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1

Objective. Nonalcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases. However, the pathogenesis of NAFLD is not still unclear. This study aims at evaluating the role of zinc finger and BTB domain-containing 7A (ZBTB7A) in NAFLD. Methods. Western blotting, real-time reverse transcription PCR (RT-PCR), and immunohistochemistry were submitted to evaluate the level of ZBTB7A in the high fatty diet- (HFD-) induced NAFLD mouse model. In vitro, the expression of ZBTB7A was assessed in oleic acid- (OA-) induced HepG2 cells with western blotting and RT-PCR. The luciferase reporter assay was used to estimate the effect of ZBTB7A on the SREBP1 and NF-κB, and the ChIP assay was subjected to evaluate the direct binding to the SREBP1 promoter. Oil Red staining was used to detect lipid accumulation, and the ELISA was used to verify the levels of TG, T-CHO, and MDA. ZBTB7A was knocked down with siRNA, and RT-PCR was performed to analyze the lipogenesis-, fatty acid transporter-, and oxidation metabolism-related genes expression. The levels of ZBTB7A in primary hepatocyte, Kupffer, and hepatic stellate cells (HSCs) were tested by RT-PCR. Results. The upregulation of ZBTB7A expression was assessed in NAFLD mice, and ZBTB7A expression was positively correlated with TNFα, IL-6, TG, T-CHO, and MDA. ZBTB7A was highly expressed in the hepatocytes. In vitro, OA-induced ZBTB7A expression and ZBTB7A expression were closely associated with SREBP1c. ZBTB7A could activate the promoter activity of SREBP1 and activate NF-κB activity. Interestingly, the direct binding of ZBTB7A in the SREBP1 promoter was acquired in HepG2 cells. Inhibition of ZBTB7A expression could attenuate OA-induced lipid accumulation, inhibit the expression of the lipogenesis-related genes and fatty acid transporter genes, and promote the expression of oxidation metabolism-related genes. Conclusion. ZBTB7A plays a significant role in the development process of NAFLD, and obesity-induced upregulation of ZBTB7A promotes lipid accumulation through activation of SREBP1 and NF-κB. ZBTB7A may be a potential novel target for the therapy of NAFLD.

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Hypoxia-induced fatty acid transporter translocation increases fatty acid transport and contributes to lipid accumulation in the heart

FEBS Letters ◽

10.1016/j.febslet.2006.05.045 ◽

2006 ◽

Vol 580 (15) ◽

pp. 3617-3623 ◽

Cited By ~ 39

Author(s):

Adrian Chabowski ◽

Jan Górski ◽

Jorge Calles-Escandon ◽

Narendra N. Tandon ◽

Arend Bonen

Keyword(s):

Fatty Acid ◽

Lipid Accumulation ◽

Fatty Acid Transport ◽

Acid Transport ◽

Fatty Acid Transporter ◽

Acid Transporter

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Human CEACAM1-LF regulates lipid storage in HepG2 cells via fatty acid transporter CD36

Journal of Biological Chemistry ◽

10.1016/j.jbc.2021.101311 ◽

2021 ◽

pp. 101311

Author(s):

Jennifer Chean ◽

Charng-jui Chen ◽

Gabriel Gugiu ◽

Patty Wong ◽

Seung Cha ◽

...

Keyword(s):

Fatty Acid ◽

Hepg2 Cells ◽

Lipid Storage ◽

Fatty Acid Transporter ◽

Acid Transporter

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Z-ligustilide and n-Butylidenephthalide Isolated from the Aerial Parts of Angelica tenuissima Inhibit Lipid Accumulation In Vitro and In Vivo

Planta Medica ◽

10.1055/a-0901-1307 ◽

2019 ◽

Vol 85 (09/10) ◽

pp. 719-728 ◽

Cited By ~ 1

Author(s):

Wonseok Lee ◽

Hye Ryoung Koo ◽

You-Jin Choi ◽

Jin Gyu Choi ◽

Myung Sook Oh ◽

...

Keyword(s):

Oleic Acid ◽

Fatty Acid ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

Target Genes ◽

Regulatory Element ◽

Fatty Acid Uptake ◽

Acid Uptake

AbstractAbnormal lipid metabolism, such as increased fatty acid uptake and esterification, is associated with nonalcoholic fatty liver disease (NAFLD). The aqueous extract of the aerial part of Angelica tenuissima Nakai (ATX) inhibited high-fat diet–induced hepatic steatosis in mice as well as oleic acid–induced neutral lipid accumulation in HepG2 cells. ATX decreased the mRNA and protein levels of CD36 and diglyceride acyltransferase 2 (DGAT2), the maturation of sterol regulatory element-binding proteins (SREBP), and the expression of the lipogenic target genes fasn and scd1. The ATX components, Z-ligustilide and n-butylidenephthalide, inhibited the expression of FATP5 and DGAT2 and thus oleic acid–induced lipid accumulation in HepG2 cells. These results suggest that ATX and its active components Z-ligustilide and n-butylidenephthalide inhibit fatty acid uptake and esterification in mice and have potential as therapeutics for NAFLD.

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Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

Viruses ◽

10.3390/v13020308 ◽

2021 ◽

Vol 13 (2) ◽

pp. 308

Author(s):

Ying-Ray Lee ◽

Chia-Ming Chang ◽

Yuan-Chieh Yeh ◽

Chi-Ying F. Huang ◽

Feng-Mao Lin ◽

...

Keyword(s):

Protein Expression ◽

Western Blotting ◽

Expression Profiles ◽

Plaque Assay ◽

Virus Titer ◽

Enterovirus 71 ◽

Luciferase Reporter ◽

Pathogen Invasion

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

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Aqueous Extract of Pepino Leaves Ameliorates Palmitic Acid-Induced Hepatocellular Lipotoxicity via Inhibition of Endoplasmic Reticulum Stress and Apoptosis

Antioxidants ◽

10.3390/antiox10060903 ◽

2021 ◽

Vol 10 (6) ◽

pp. 903

Author(s):

Jen-Ying Hsu ◽

Hui-Hsuan Lin ◽

Charng-Cherng Chyau ◽

Zhi-Hong Wang ◽

Jing-Hsien Chen

Keyword(s):

Fatty Acid ◽

Palmitic Acid ◽

Er Stress ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

Target Genes ◽

Liver Lipid ◽

Antioxidant Response ◽

Long Chain Fatty Acid ◽

Nrf2 Expression

Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.

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An in vitro model for essential fatty acid deficiency: HepG2 cells permanently maintained in lipid-free medium.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)41394-x ◽

1992 ◽

Vol 33 (11) ◽

pp. 1719-1726

Author(s):

EE Furth ◽

H Sprecher ◽

EA Fisher ◽

HD Fleishman ◽

M Laposata

Keyword(s):

Fatty Acid ◽

Essential Fatty Acid ◽

Hepg2 Cells ◽

Essential Fatty Acid Deficiency ◽

In Vitro Model ◽

Free Medium ◽

Acid Deficiency ◽

Vitro Model ◽

Fatty Acid Deficiency

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Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.1080/14767058.2017.1397119 ◽

2017 ◽

Vol 32 (6) ◽

pp. 971-978 ◽

Cited By ~ 2

Author(s):

Xiaohua Yang ◽

Patricia Glazebrook ◽

Geraldine C. Ranasinghe ◽

Maricela Haghiac ◽

Virtu Calabuig-Navarro ◽

...

Keyword(s):

Endothelial Cells ◽

Fatty Acid ◽

Obese Women ◽

Fatty Acid Transporter ◽

Acid Transporter ◽

Transporter Expression

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CircRNA PIP5K1A promotes the progression of glioma through upregulation of TCF12/PI3K/AKT pathway by sponging miR-515-5p

10.21203/rs.3.rs-49985/v1 ◽

2020 ◽

Author(s):

Kebin Zheng ◽

Haipeng Xie ◽

Xiaosong Wu ◽

Xichao Wen ◽

Zhaomu Zeng ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

Cell Model ◽

Luciferase Reporter ◽

Akt Pathway ◽

Circular Rnas ◽

Rt Pcr ◽

Mesenchymal Transition ◽

Normal Tissues

Abstract BackgroundIncreasing studies have revealed that circular RNAs (CircRNAs) make great contribution to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A in glioma. MethodsFirstly, RT-PCR was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and a cell model of CircPIP5K1A overexpression and knockdown was constructed. Subsequently, cell proliferation and viability were detected by CCK8 method and BrdU staining, apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (including Caspase3, Bax and Bcl2) and epithelial-mesenchymal transition (EMT) markers (including E-cadherin, Vimentin and N-cadherin) by western blot or RT-PCR. ResultsThe results manifested that CircPIP5K1A was obviously upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was distinctly related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated the proliferation, invasion, EMT of glioma cells, and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A also upregulated TCF12 and PI3K/AKT pathway activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while dual luciferase reporter assay and RNA immunocoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3'-untranslated region (UTR) of TCF12. ConclusionsAltogether, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates the development of glioma through the modulating miR-515-5p mediated TCF12/PI3K/AKT axis.

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Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/321407 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Hiroe Go ◽

Jin Ah Ryuk ◽

Hye Won Lee ◽

In Sil Park ◽

Ki-Jung Kil ◽

...

Keyword(s):

Lipid Accumulation ◽

Hepg2 Cells ◽

Cholesterol Synthesis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Protein Levels ◽

Related Disease

The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. Inin vivostudy using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activityin vitro. These observations support the idea that Sagunja-tang is bioavailable bothin vivoandin vitroand could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.

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