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Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats
Background The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Wes...
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Published in: | Lipids in health and disease 2020-08, Vol.19 (1), p.1-192, Article 192 |
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description | Background The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol. Keywords: Western diet, Plasma cholesterol, Lipogenesis, Hepatic steatosis, Liver cholesterol metabolism, Low-density lipoprotein-receptor, Proprotein convertase subtilisin/kexin 9 |
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Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol. Keywords: Western diet, Plasma cholesterol, Lipogenesis, Hepatic steatosis, Liver cholesterol metabolism, Low-density lipoprotein-receptor, Proprotein convertase subtilisin/kexin 9]]></description><identifier>ISSN: 1476-511X</identifier><identifier>EISSN: 1476-511X</identifier><identifier>DOI: 10.1186/s12944-020-01351-2</identifier><identifier>PMID: 32825820</identifier><language>eng</language><publisher>London: BioMed Central Ltd</publisher><subject>Abdomen ; Acetyl-CoA carboxylase ; Acyltransferase ; Bile ; Blood cholesterol ; Carbohydrates ; Cholesterol ; Cholesterol tests ; Diet ; EDTA ; Fat metabolism ; Fatty acids ; Fructose ; Gene expression ; Glucose ; Hepatic steatosis ; High fat diet ; Hypotheses ; Kexin ; Lipid metabolism ; Lipids ; Lipogenesis ; Liver ; Liver cholesterol metabolism ; Low density lipoprotein ; Low density lipoproteins ; Low-density lipoprotein-receptor ; Metabolism ; mRNA ; Physiological aspects ; Plasma ; Plasma cholesterol ; Proprotein convertases ; Protein binding ; Proteins ; Receptor density ; Sterol regulatory element-binding protein ; Subtilisin ; Sucrose ; Triglycerides ; Western diet</subject><ispartof>Lipids in health and disease, 2020-08, Vol.19 (1), p.1-192, Article 192</ispartof><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-452d083e6a0fb7263132f080dedeb08d74ab511db00d4c120be4631d906095fb3</citedby><cites>FETCH-LOGICAL-c540t-452d083e6a0fb7263132f080dedeb08d74ab511db00d4c120be4631d906095fb3</cites><orcidid>0000-0003-3091-0753</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442981/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2444116069?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids></links><search><creatorcontrib>St-Amand, Roxane</creatorcontrib><creatorcontrib>Ngo Sock, Émilienne T</creatorcontrib><creatorcontrib>Quinn, Samantha</creatorcontrib><creatorcontrib>Lavoie, Jean-Marc</creatorcontrib><creatorcontrib>St-Pierre, David H</creatorcontrib><title>Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats</title><title>Lipids in health and disease</title><description><![CDATA[Background The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol. Keywords: Western diet, Plasma cholesterol, Lipogenesis, Hepatic steatosis, Liver cholesterol metabolism, Low-density lipoprotein-receptor, Proprotein convertase subtilisin/kexin 9]]></description><subject>Abdomen</subject><subject>Acetyl-CoA carboxylase</subject><subject>Acyltransferase</subject><subject>Bile</subject><subject>Blood cholesterol</subject><subject>Carbohydrates</subject><subject>Cholesterol</subject><subject>Cholesterol tests</subject><subject>Diet</subject><subject>EDTA</subject><subject>Fat metabolism</subject><subject>Fatty acids</subject><subject>Fructose</subject><subject>Gene expression</subject><subject>Glucose</subject><subject>Hepatic steatosis</subject><subject>High fat diet</subject><subject>Hypotheses</subject><subject>Kexin</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Lipogenesis</subject><subject>Liver</subject><subject>Liver cholesterol metabolism</subject><subject>Low density lipoprotein</subject><subject>Low density lipoproteins</subject><subject>Low-density lipoprotein-receptor</subject><subject>Metabolism</subject><subject>mRNA</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Plasma cholesterol</subject><subject>Proprotein convertases</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Receptor density</subject><subject>Sterol regulatory element-binding protein</subject><subject>Subtilisin</subject><subject>Sucrose</subject><subject>Triglycerides</subject><subject>Western 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Jean-Marc</creator><creator>St-Pierre, David H</creator><general>BioMed Central Ltd</general><general>BioMed 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in rats</title><author>St-Amand, Roxane ; Ngo Sock, Émilienne T ; Quinn, Samantha ; Lavoie, Jean-Marc ; St-Pierre, David H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-452d083e6a0fb7263132f080dedeb08d74ab511db00d4c120be4631d906095fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abdomen</topic><topic>Acetyl-CoA carboxylase</topic><topic>Acyltransferase</topic><topic>Bile</topic><topic>Blood cholesterol</topic><topic>Carbohydrates</topic><topic>Cholesterol</topic><topic>Cholesterol tests</topic><topic>Diet</topic><topic>EDTA</topic><topic>Fat metabolism</topic><topic>Fatty acids</topic><topic>Fructose</topic><topic>Gene expression</topic><topic>Glucose</topic><topic>Hepatic steatosis</topic><topic>High fat diet</topic><topic>Hypotheses</topic><topic>Kexin</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Lipogenesis</topic><topic>Liver</topic><topic>Liver cholesterol metabolism</topic><topic>Low density lipoprotein</topic><topic>Low density lipoproteins</topic><topic>Low-density lipoprotein-receptor</topic><topic>Metabolism</topic><topic>mRNA</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Plasma cholesterol</topic><topic>Proprotein convertases</topic><topic>Protein binding</topic><topic>Proteins</topic><topic>Receptor density</topic><topic>Sterol regulatory element-binding protein</topic><topic>Subtilisin</topic><topic>Sucrose</topic><topic>Triglycerides</topic><topic>Western diet</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>St-Amand, Roxane</creatorcontrib><creatorcontrib>Ngo Sock, Émilienne T</creatorcontrib><creatorcontrib>Quinn, Samantha</creatorcontrib><creatorcontrib>Lavoie, Jean-Marc</creatorcontrib><creatorcontrib>St-Pierre, David 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Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Lipids in health and disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>St-Amand, Roxane</au><au>Ngo Sock, Émilienne T</au><au>Quinn, Samantha</au><au>Lavoie, Jean-Marc</au><au>St-Pierre, David H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats</atitle><jtitle>Lipids in health and disease</jtitle><date>2020-08-21</date><risdate>2020</risdate><volume>19</volume><issue>1</issue><spage>1</spage><epage>192</epage><pages>1-192</pages><artnum>192</artnum><issn>1476-511X</issn><eissn>1476-511X</eissn><abstract><![CDATA[Background The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol. Keywords: Western diet, Plasma cholesterol, Lipogenesis, Hepatic steatosis, Liver cholesterol metabolism, Low-density lipoprotein-receptor, Proprotein convertase subtilisin/kexin 9]]></abstract><cop>London</cop><pub>BioMed Central Ltd</pub><pmid>32825820</pmid><doi>10.1186/s12944-020-01351-2</doi><orcidid>https://orcid.org/0000-0003-3091-0753</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Abdomen Acetyl-CoA carboxylase Acyltransferase Bile Blood cholesterol Carbohydrates Cholesterol Cholesterol tests Diet EDTA Fat metabolism Fatty acids Fructose Gene expression Glucose Hepatic steatosis High fat diet Hypotheses Kexin Lipid metabolism Lipids Lipogenesis Liver Liver cholesterol metabolism Low density lipoprotein Low density lipoproteins Low-density lipoprotein-receptor Metabolism mRNA Physiological aspects Plasma Plasma cholesterol Proprotein convertases Protein binding Proteins Receptor density Sterol regulatory element-binding protein Subtilisin Sucrose Triglycerides Western diet |
title | Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats |
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