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Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing as obesity and diabetes become more common. There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypo...
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Published in: | Evidence-based complementary and alternative medicine 2022-11, Vol.2022, p.1-13 |
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description | The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing as obesity and diabetes become more common. There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypolipidemic and hepatoprotective effects. This study tried to interpret the pharmacology and molecular mechanisms of QGD in NAFLD rats. Firstly, the therapeutic effects of QGD on high-fat diet (HFD)-induced NAFLD rats were evaluated. Then, integration of lipidomics and transcriptomics was conducted to explore the possible pathways and targets of QGD against NAFLD. QGD at low dosage (QGL) administration reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (P |
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There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypolipidemic and hepatoprotective effects. This study tried to interpret the pharmacology and molecular mechanisms of QGD in NAFLD rats. Firstly, the therapeutic effects of QGD on high-fat diet (HFD)-induced NAFLD rats were evaluated. Then, integration of lipidomics and transcriptomics was conducted to explore the possible pathways and targets of QGD against NAFLD. QGD at low dosage (QGL) administration reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (P<0.05). Liver histopathology indicated that QGL could alleviate hepatic steatosis. The main differential lipids (DELs) affected by QGD were glycerolipids. KEGG enrichment analysis suggested that the main pathways by which QGD improved NAFLD may be cholesterol metabolism, glycerolipid metabolism, and insulin resistance. Transcriptome sequencing identified 179 upregulated and 194 downregulated mRNAs after QGD treatment. An interaction network based on DELs and differential genes (DEGs) suggested that QGD inhibited hepatic steatosis mainly by reducing hepatic insulin resistance and triglyceride biosynthesis via the PPP1R3C/SIK1/CRTC2 and PPP1R3C/SIK1/SREBP1 signal axis, respectively. These findings indicated that QGD could protect against NAFLD induced by HFD. The improvement of hepatic insulin resistance and the reduction of triglyceride biosynthesis might be the potential mechanisms.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2022/9739032</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>Biosynthesis ; Chinese medicine ; Cholesterol ; Diabetes mellitus ; Disease ; Drug dosages ; Fatty acids ; Fatty liver ; Gene expression ; Glucose ; High fat diet ; Hyperlipidemia ; Insulin ; Insulin resistance ; Laboratory animals ; Lipid metabolism ; Lipids ; Liver ; Liver diseases ; Low density lipoprotein ; Metabolism ; Metabolites ; Molecular modelling ; Pharmaceutical industry ; Steatosis ; Traditional Chinese medicine ; Transcriptomes ; Transcriptomics</subject><ispartof>Evidence-based complementary and alternative medicine, 2022-11, Vol.2022, p.1-13</ispartof><rights>Copyright © 2022 Simin Fan et al.</rights><rights>Copyright © 2022 Simin Fan et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2022 Simin Fan et al. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-246d45f9ad712d20090be6a009d5a4815ff9b62cc6f8aca43f619633af7ebb8a3</citedby><cites>FETCH-LOGICAL-c425t-246d45f9ad712d20090be6a009d5a4815ff9b62cc6f8aca43f619633af7ebb8a3</cites><orcidid>0000-0003-4546-0003 ; 0000-0003-2056-261X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2745657218/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2745657218?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,25753,27924,27925,37012,37013,44590,75126</link.rule.ids></links><search><contributor>Hassan, Waseem</contributor><contributor>Waseem Hassan</contributor><creatorcontrib>Fan, Simin</creatorcontrib><creatorcontrib>Zhou, Zunming</creatorcontrib><creatorcontrib>Ye, Jintong</creatorcontrib><creatorcontrib>Li, Yanfang</creatorcontrib><creatorcontrib>Huang, Keer</creatorcontrib><creatorcontrib>Ke, Xuehong</creatorcontrib><title>Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD</title><title>Evidence-based complementary and alternative medicine</title><description>The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing as obesity and diabetes become more common. There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypolipidemic and hepatoprotective effects. This study tried to interpret the pharmacology and molecular mechanisms of QGD in NAFLD rats. Firstly, the therapeutic effects of QGD on high-fat diet (HFD)-induced NAFLD rats were evaluated. Then, integration of lipidomics and transcriptomics was conducted to explore the possible pathways and targets of QGD against NAFLD. QGD at low dosage (QGL) administration reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (P<0.05). Liver histopathology indicated that QGL could alleviate hepatic steatosis. The main differential lipids (DELs) affected by QGD were glycerolipids. KEGG enrichment analysis suggested that the main pathways by which QGD improved NAFLD may be cholesterol metabolism, glycerolipid metabolism, and insulin resistance. Transcriptome sequencing identified 179 upregulated and 194 downregulated mRNAs after QGD treatment. An interaction network based on DELs and differential genes (DEGs) suggested that QGD inhibited hepatic steatosis mainly by reducing hepatic insulin resistance and triglyceride biosynthesis via the PPP1R3C/SIK1/CRTC2 and PPP1R3C/SIK1/SREBP1 signal axis, respectively. These findings indicated that QGD could protect against NAFLD induced by HFD. The improvement of hepatic insulin resistance and the reduction of triglyceride biosynthesis might be the potential mechanisms.</description><subject>Biosynthesis</subject><subject>Chinese medicine</subject><subject>Cholesterol</subject><subject>Diabetes mellitus</subject><subject>Disease</subject><subject>Drug dosages</subject><subject>Fatty acids</subject><subject>Fatty liver</subject><subject>Gene expression</subject><subject>Glucose</subject><subject>High fat diet</subject><subject>Hyperlipidemia</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Laboratory animals</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Low density lipoprotein</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Molecular modelling</subject><subject>Pharmaceutical industry</subject><subject>Steatosis</subject><subject>Traditional Chinese medicine</subject><subject>Transcriptomes</subject><subject>Transcriptomics</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp9kctKxDAUhosoeN35AAU3go4maS7NRpDxCqOiKLgLp2kyE50mY9JRfHs7dhB04eoPyZePc_izbBejI4wZOyaIkGMpCokKspJtYEHxgJKyXP05i-f1bDOlF4SIFEJsZK_XvjXjCK0LPg82H7mZq0PjdMrB1_ljBJ90dLO2v3sw7wamKW8nJj-31mnQn9_gjdET8C41C8m9G5v8zOige63Pb08vRmfb2ZrtPpudZW5lTxfnj8Orweju8np4OhpoSlg7IJTXlFkJtcCkJghJVBkOXdYMaImZtbLiRGtuS9BAC8ux5EUBVpiqKqHYyk5672xeNabWxrcRpmoWXQPxUwVw6veLdxM1Du9KCsRQSTvB_lIQw9vcpFY1LmkznYI3YZ4UEZRyzmUpOnTvD_oS5tF36y0oxpkguOyow57SMaQUjf0ZBiO1qE4tqlPL6jr8oMcnztfw4f6nvwBSR5mb</recordid><startdate>20221121</startdate><enddate>20221121</enddate><creator>Fan, Simin</creator><creator>Zhou, Zunming</creator><creator>Ye, Jintong</creator><creator>Li, Yanfang</creator><creator>Huang, Keer</creator><creator>Ke, Xuehong</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4546-0003</orcidid><orcidid>https://orcid.org/0000-0003-2056-261X</orcidid></search><sort><creationdate>20221121</creationdate><title>Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD</title><author>Fan, Simin ; 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There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypolipidemic and hepatoprotective effects. This study tried to interpret the pharmacology and molecular mechanisms of QGD in NAFLD rats. Firstly, the therapeutic effects of QGD on high-fat diet (HFD)-induced NAFLD rats were evaluated. Then, integration of lipidomics and transcriptomics was conducted to explore the possible pathways and targets of QGD against NAFLD. QGD at low dosage (QGL) administration reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (P<0.05). Liver histopathology indicated that QGL could alleviate hepatic steatosis. The main differential lipids (DELs) affected by QGD were glycerolipids. KEGG enrichment analysis suggested that the main pathways by which QGD improved NAFLD may be cholesterol metabolism, glycerolipid metabolism, and insulin resistance. Transcriptome sequencing identified 179 upregulated and 194 downregulated mRNAs after QGD treatment. An interaction network based on DELs and differential genes (DEGs) suggested that QGD inhibited hepatic steatosis mainly by reducing hepatic insulin resistance and triglyceride biosynthesis via the PPP1R3C/SIK1/CRTC2 and PPP1R3C/SIK1/SREBP1 signal axis, respectively. These findings indicated that QGD could protect against NAFLD induced by HFD. The improvement of hepatic insulin resistance and the reduction of triglyceride biosynthesis might be the potential mechanisms.</abstract><cop>New York</cop><pub>Hindawi</pub><doi>10.1155/2022/9739032</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-4546-0003</orcidid><orcidid>https://orcid.org/0000-0003-2056-261X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biosynthesis Chinese medicine Cholesterol Diabetes mellitus Disease Drug dosages Fatty acids Fatty liver Gene expression Glucose High fat diet Hyperlipidemia Insulin Insulin resistance Laboratory animals Lipid metabolism Lipids Liver Liver diseases Low density lipoprotein Metabolism Metabolites Molecular modelling Pharmaceutical industry Steatosis Traditional Chinese medicine Transcriptomes Transcriptomics |
title | Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD |
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