Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway
This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rat...
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| description | This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed. Enzyme linked immunosorbent assay was used to determine serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase (SOD), malondialdehyde (MDA), and T-AOC contents. Hematoxylin-eosin staining and oil red O staining were utilized to observe the histological changes in the liver. Biochemical method was applied to measure serum ALT and AST changes. Western blot assay and qRT-PCR were employed to detect the changes in SIRT1/FOXO1 pathway-related proteins, cholesterol synthesis-related genes, and SREBP-2. EGCG 50 mg/kg could obviously decrease the liver weight and liver coefficient, reduce serum TG, TC, LDL-C, and FFA levels (
P
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| doi_str_mv | 10.1007/s11010-018-3324-x |
| format | Article |
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P
< 0.05), and increase serum HDL-C levels in hyperlipidemic rats. EGCG could diminish hyperlipidemia-induced liver injury and reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Oil red O staining results demonstrated that the number of red lipid droplets in hepatocytes reduced to varying degrees, especially high-dose EGCG. EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity. In the model group, SIRT1 expression increased, and FOXO1 expression decreased. EGCG activated SIRT1 and increased FOXO1 expression, whose expression trend was consistent with the fenofibrate group. HMGCR, FDPS, SS, and ABCA1 expression increased, and ACAT2 expression noticeably reduced in SREBP-2
+/+
transgenic rats. EGCG could reverse the expression trend of each gene. Simultaneously, EGCG increased FOXO1 expression, and decrease SREBP-2 expression; however, no significant changes in these expression were found in SREBP-2
−/−
rats. EGCG can alleviate liver injury and oxidative stress in hyperlipidemic rats. EGCG can activate SIRT1, activate FOXO1 protein, regulate SREBP-2 protein, and inhibit hepatic cholesterol synthesis.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-018-3324-x</identifier><identifier>PMID: 29446047</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>ABCA1 protein ; Alanine ; Alanine transaminase ; Animal models ; Aspartate ; Aspartate aminotransferase ; ATP-binding protein ; Biochemistry ; Biomedical and Life Sciences ; Cardiology ; Catechin ; Change detection ; Chemical synthesis ; Cholesterol ; Enzyme-linked immunosorbent assay ; Enzymes ; Epigallocatechin gallate ; Fenofibrate ; FOXO1 protein ; Gene expression ; Genetic engineering ; Hepatocytes ; High density lipoprotein ; Hypercholesterolemia ; Hyperlipidemia ; Injury prevention ; Life Sciences ; Lipids ; Liver ; Low density lipoprotein ; Low density lipoproteins ; Malondialdehyde ; Medical Biochemistry ; Oncology ; Oxidative stress ; Proteins ; Rats ; Rodents ; Signal transduction ; Signaling ; SIRT1 protein ; Staining ; Superoxide dismutase ; Superoxides ; Transcription ; Weight reduction</subject><ispartof>Molecular and cellular biochemistry, 2018-11, Vol.448 (1-2), p.175-185</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Springer</rights><rights>Molecular and Cellular Biochemistry is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-2b0957f1c3784aecf81acb8692ba7784ed066a8394076cfc1776355213f2e1a93</citedby><cites>FETCH-LOGICAL-c439t-2b0957f1c3784aecf81acb8692ba7784ed066a8394076cfc1776355213f2e1a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-018-3324-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-018-3324-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29446047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yongnan</creatorcontrib><creatorcontrib>Wu, Shuodong</creatorcontrib><title>Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed. Enzyme linked immunosorbent assay was used to determine serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase (SOD), malondialdehyde (MDA), and T-AOC contents. Hematoxylin-eosin staining and oil red O staining were utilized to observe the histological changes in the liver. Biochemical method was applied to measure serum ALT and AST changes. Western blot assay and qRT-PCR were employed to detect the changes in SIRT1/FOXO1 pathway-related proteins, cholesterol synthesis-related genes, and SREBP-2. EGCG 50 mg/kg could obviously decrease the liver weight and liver coefficient, reduce serum TG, TC, LDL-C, and FFA levels (
P
< 0.05), and increase serum HDL-C levels in hyperlipidemic rats. EGCG could diminish hyperlipidemia-induced liver injury and reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Oil red O staining results demonstrated that the number of red lipid droplets in hepatocytes reduced to varying degrees, especially high-dose EGCG. EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity. In the model group, SIRT1 expression increased, and FOXO1 expression decreased. EGCG activated SIRT1 and increased FOXO1 expression, whose expression trend was consistent with the fenofibrate group. HMGCR, FDPS, SS, and ABCA1 expression increased, and ACAT2 expression noticeably reduced in SREBP-2
+/+
transgenic rats. EGCG could reverse the expression trend of each gene. Simultaneously, EGCG increased FOXO1 expression, and decrease SREBP-2 expression; however, no significant changes in these expression were found in SREBP-2
−/−
rats. EGCG can alleviate liver injury and oxidative stress in hyperlipidemic rats. EGCG can activate SIRT1, activate FOXO1 protein, regulate SREBP-2 protein, and inhibit hepatic cholesterol synthesis.</description><subject>ABCA1 protein</subject><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Animal models</subject><subject>Aspartate</subject><subject>Aspartate aminotransferase</subject><subject>ATP-binding protein</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cardiology</subject><subject>Catechin</subject><subject>Change detection</subject><subject>Chemical synthesis</subject><subject>Cholesterol</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Epigallocatechin gallate</subject><subject>Fenofibrate</subject><subject>FOXO1 protein</subject><subject>Gene expression</subject><subject>Genetic engineering</subject><subject>Hepatocytes</subject><subject>High density lipoprotein</subject><subject>Hypercholesterolemia</subject><subject>Hyperlipidemia</subject><subject>Injury prevention</subject><subject>Life Sciences</subject><subject>Lipids</subject><subject>Liver</subject><subject>Low density lipoprotein</subject><subject>Low density lipoproteins</subject><subject>Malondialdehyde</subject><subject>Medical Biochemistry</subject><subject>Oncology</subject><subject>Oxidative stress</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>SIRT1 protein</subject><subject>Staining</subject><subject>Superoxide dismutase</subject><subject>Superoxides</subject><subject>Transcription</subject><subject>Weight reduction</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kUFv1DAQhS0EokvhB3BBlrhwSeuxnTg5lmoLlSotaovEzfJ6J4mrbBzsRO1K_HgcpVCBQD7YHn_zNM-PkLfAToAxdRoBGLCMQZkJwWX28IysIFcikxVUz8mKCcayEpQ6Iq9ivGMJZgAvyRGvpCyYVCvyYz24xnSdt2ZE27qezrd0pnEahoAxYqQtDmZ0ltrWdxhHDL6j8dCPLUYX6fZARxMaHF3f0Jvr9ccvGadjG_zUtPTm8voWTi823zZAo2t6081UkmvvzeE1eVGbLuKbx_2YfL1Y355_zq42ny7Pz64yK0U1ZnzLqlzVYIUqpUFbl2DstiwqvjUqlXDHisKUopJMFba2yXAh8pyDqDmCqcQx-bDoDsF_n5IDvXfRYvLZo5-i5oxxqUol84S-_wu981NIYy8UQJELeKLSZ6F2fe3HYOwsqs_yvOCyZKVK1Mk_qLR2uHfW91i7VP-jAZYGG3yMAWs9BLc34aCB6TlxvSSuU-J6Tlw_pJ53jwNP2z3ufnf8ijgBfAFieuobDE-O_q_6E2xotNw</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Li, 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B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20181101</creationdate><title>Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway</title><author>Li, Yongnan ; Wu, Shuodong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-2b0957f1c3784aecf81acb8692ba7784ed066a8394076cfc1776355213f2e1a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>ABCA1 protein</topic><topic>Alanine</topic><topic>Alanine transaminase</topic><topic>Animal models</topic><topic>Aspartate</topic><topic>Aspartate aminotransferase</topic><topic>ATP-binding protein</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cardiology</topic><topic>Catechin</topic><topic>Change detection</topic><topic>Chemical synthesis</topic><topic>Cholesterol</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Enzymes</topic><topic>Epigallocatechin gallate</topic><topic>Fenofibrate</topic><topic>FOXO1 protein</topic><topic>Gene expression</topic><topic>Genetic engineering</topic><topic>Hepatocytes</topic><topic>High density lipoprotein</topic><topic>Hypercholesterolemia</topic><topic>Hyperlipidemia</topic><topic>Injury prevention</topic><topic>Life Sciences</topic><topic>Lipids</topic><topic>Liver</topic><topic>Low density lipoprotein</topic><topic>Low density lipoproteins</topic><topic>Malondialdehyde</topic><topic>Medical Biochemistry</topic><topic>Oncology</topic><topic>Oxidative stress</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>SIRT1 protein</topic><topic>Staining</topic><topic>Superoxide dismutase</topic><topic>Superoxides</topic><topic>Transcription</topic><topic>Weight reduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yongnan</creatorcontrib><creatorcontrib>Wu, Shuodong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research 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cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yongnan</au><au>Wu, Shuodong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway</atitle><jtitle>Molecular and cellular biochemistry</jtitle><stitle>Mol Cell Biochem</stitle><addtitle>Mol Cell Biochem</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>448</volume><issue>1-2</issue><spage>175</spage><epage>185</epage><pages>175-185</pages><issn>0300-8177</issn><eissn>1573-4919</eissn><abstract>This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed. Enzyme linked immunosorbent assay was used to determine serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase (SOD), malondialdehyde (MDA), and T-AOC contents. Hematoxylin-eosin staining and oil red O staining were utilized to observe the histological changes in the liver. Biochemical method was applied to measure serum ALT and AST changes. Western blot assay and qRT-PCR were employed to detect the changes in SIRT1/FOXO1 pathway-related proteins, cholesterol synthesis-related genes, and SREBP-2. EGCG 50 mg/kg could obviously decrease the liver weight and liver coefficient, reduce serum TG, TC, LDL-C, and FFA levels (
P
< 0.05), and increase serum HDL-C levels in hyperlipidemic rats. EGCG could diminish hyperlipidemia-induced liver injury and reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Oil red O staining results demonstrated that the number of red lipid droplets in hepatocytes reduced to varying degrees, especially high-dose EGCG. EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity. In the model group, SIRT1 expression increased, and FOXO1 expression decreased. EGCG activated SIRT1 and increased FOXO1 expression, whose expression trend was consistent with the fenofibrate group. HMGCR, FDPS, SS, and ABCA1 expression increased, and ACAT2 expression noticeably reduced in SREBP-2
+/+
transgenic rats. EGCG could reverse the expression trend of each gene. Simultaneously, EGCG increased FOXO1 expression, and decrease SREBP-2 expression; however, no significant changes in these expression were found in SREBP-2
−/−
rats. EGCG can alleviate liver injury and oxidative stress in hyperlipidemic rats. EGCG can activate SIRT1, activate FOXO1 protein, regulate SREBP-2 protein, and inhibit hepatic cholesterol synthesis.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29446047</pmid><doi>10.1007/s11010-018-3324-x</doi><tpages>11</tpages></addata></record> |
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| subjects | ABCA1 protein Alanine Alanine transaminase Animal models Aspartate Aspartate aminotransferase ATP-binding protein Biochemistry Biomedical and Life Sciences Cardiology Catechin Change detection Chemical synthesis Cholesterol Enzyme-linked immunosorbent assay Enzymes Epigallocatechin gallate Fenofibrate FOXO1 protein Gene expression Genetic engineering Hepatocytes High density lipoprotein Hypercholesterolemia Hyperlipidemia Injury prevention Life Sciences Lipids Liver Low density lipoprotein Low density lipoproteins Malondialdehyde Medical Biochemistry Oncology Oxidative stress Proteins Rats Rodents Signal transduction Signaling SIRT1 protein Staining Superoxide dismutase Superoxides Transcription Weight reduction |
| title | Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway |
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