Treatment of preestablished diet-induced fatty liver by oral fatty acid–bile acid conjugates in rodents
BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid–bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents. AIMThis study was undertaken to test whether ora...
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| Veröffentlicht in: | European journal of gastroenterology & hepatology 2008-12, Vol.20 (12), p.1205-1213 |
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| container_title | European journal of gastroenterology & hepatology |
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| creator | Leikin-Frenkel, Alicia Goldiner, Ilana Leikin-Gobbi, Diana Rosenberg, Ruth Bonen, Hamutal Litvak, Alex Bernheim, Joelle Konikoff, Fred M Gilat, Tuvia |
| description | BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid–bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents.
AIMThis study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD.
METHODSNAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids.
RESULTSFABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P |
| doi_str_mv | 10.1097/MEG.0b013e3282fc9743 |
| format | Article |
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AIMThis study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD.
METHODSNAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids.
RESULTSFABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P<0.03). Diglycerides (P<0.003) and triglycerides (P<0.01) were the main neutral liver lipids that decreased during FABAC therapy. Both FABACs tested reduced liver fat in NAFLD at doses of 25 and 150 mg/kg/day. High-fat diet increased, whereas FABAC therapy decreased plasma 16 : 1/(16 : 0+16 : 1) fatty acid ratio – a marker of stearoyl CoA desaturase activity. In HepG2 cells FABACs decreased de-novo fatty acid synthesis dose dependently.
CONCLUSIONOral FABAC therapy decreased liver fat in preestablished NAFLD in mice and rats. Inhibition of stearoyl CoA desaturase activity and fatty acid synthesis are mechanisms that may contribute to this decrease. FABACs may be potential therapeutic agents for human NAFLD.</description><identifier>ISSN: 0954-691X</identifier><identifier>EISSN: 1473-5687</identifier><identifier>DOI: 10.1097/MEG.0b013e3282fc9743</identifier><identifier>PMID: 18989145</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Animals ; Bile Acids and Salts - therapeutic use ; Biological and medical sciences ; Blood Glucose - metabolism ; Cholic Acids - therapeutic use ; Dietary Fats - administration & dosage ; Dietary Fats - adverse effects ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Fatty Acids - biosynthesis ; Fatty Acids - therapeutic use ; Fatty Liver - drug therapy ; Fatty Liver - etiology ; Fatty Liver - metabolism ; Fatty Liver - pathology ; Gastroenterology. Liver. Pancreas. Abdomen ; Lipid Metabolism ; Liver - metabolism ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Metabolic diseases ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Miscellaneous ; Other diseases. Semiology ; Other metabolic disorders ; Rats ; Rats, Inbred F344 ; Stearoyl-CoA Desaturase - blood ; Weight Gain</subject><ispartof>European journal of gastroenterology & hepatology, 2008-12, Vol.20 (12), p.1205-1213</ispartof><rights>2008 Lippincott Williams & Wilkins, Inc.</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3291-2c25582f2c0a014f44fbaf4ec8c2581c1df5a9997e4b6405f6c9300951ba50643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20804903$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18989145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leikin-Frenkel, Alicia</creatorcontrib><creatorcontrib>Goldiner, Ilana</creatorcontrib><creatorcontrib>Leikin-Gobbi, Diana</creatorcontrib><creatorcontrib>Rosenberg, Ruth</creatorcontrib><creatorcontrib>Bonen, Hamutal</creatorcontrib><creatorcontrib>Litvak, Alex</creatorcontrib><creatorcontrib>Bernheim, Joelle</creatorcontrib><creatorcontrib>Konikoff, Fred M</creatorcontrib><creatorcontrib>Gilat, Tuvia</creatorcontrib><title>Treatment of preestablished diet-induced fatty liver by oral fatty acid–bile acid conjugates in rodents</title><title>European journal of gastroenterology & hepatology</title><addtitle>Eur J Gastroenterol Hepatol</addtitle><description>BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid–bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents.
AIMThis study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD.
METHODSNAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids.
RESULTSFABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P<0.03). Diglycerides (P<0.003) and triglycerides (P<0.01) were the main neutral liver lipids that decreased during FABAC therapy. Both FABACs tested reduced liver fat in NAFLD at doses of 25 and 150 mg/kg/day. High-fat diet increased, whereas FABAC therapy decreased plasma 16 : 1/(16 : 0+16 : 1) fatty acid ratio – a marker of stearoyl CoA desaturase activity. In HepG2 cells FABACs decreased de-novo fatty acid synthesis dose dependently.
CONCLUSIONOral FABAC therapy decreased liver fat in preestablished NAFLD in mice and rats. Inhibition of stearoyl CoA desaturase activity and fatty acid synthesis are mechanisms that may contribute to this decrease. FABACs may be potential therapeutic agents for human NAFLD.</description><subject>Animals</subject><subject>Bile Acids and Salts - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Cholic Acids - therapeutic use</subject><subject>Dietary Fats - administration & dosage</subject><subject>Dietary Fats - adverse effects</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Fatty Acids - biosynthesis</subject><subject>Fatty Acids - therapeutic use</subject><subject>Fatty Liver - drug therapy</subject><subject>Fatty Liver - etiology</subject><subject>Fatty Liver - metabolism</subject><subject>Fatty Liver - pathology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Lipid Metabolism</subject><subject>Liver - metabolism</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Miscellaneous</subject><subject>Other diseases. Semiology</subject><subject>Other metabolic disorders</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Stearoyl-CoA Desaturase - blood</subject><subject>Weight Gain</subject><issn>0954-691X</issn><issn>1473-5687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkM9uFSEUxomxsdfqGxjDRnfTHv7MAEvT1GpS001N3E0Y5uClcmeuwNjcne_gG_ZJRDuxiQsOHPidj3wfIa8YnDIw6uzTxeUpDMAECq65d0ZJ8YRsmFSiaTutnpINmFY2nWFfjsnznG8BmBJMPSPHTBttmGw3JNwktGWHU6Gzp_uEmIsdYshbHOkYsDRhGhdXG29LOdAYfmCiw4HOycb1zrow3v_8NYSIf8_UzdPt8tUWzDRMNM1jlc8vyJG3MePLdT8hn99f3Jx_aK6uLz-ev7tqnOCGNdzxtq1-uAMLTHop_WC9RKfrg2aOjb61xhiFcugktL5zRkB1ygbbQifFCXn7oLtP8_el2ul3ITuM0U44L7nvjOqk7ngF5QPo0pxzQt_vU9jZdOgZ9H8i7mvE_f8R17HXq_4y7HB8HFozrcCbFbDZ2eiTnVzI_zgOGqQB8fj_3RwLpvwtLneY-i3aWLY9AEiuhGo4gGa1QFMXY-I3lSGWsw</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Leikin-Frenkel, Alicia</creator><creator>Goldiner, Ilana</creator><creator>Leikin-Gobbi, Diana</creator><creator>Rosenberg, Ruth</creator><creator>Bonen, Hamutal</creator><creator>Litvak, Alex</creator><creator>Bernheim, Joelle</creator><creator>Konikoff, Fred M</creator><creator>Gilat, Tuvia</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200812</creationdate><title>Treatment of preestablished diet-induced fatty liver by oral fatty acid–bile acid conjugates in rodents</title><author>Leikin-Frenkel, Alicia ; Goldiner, Ilana ; Leikin-Gobbi, Diana ; Rosenberg, Ruth ; Bonen, Hamutal ; Litvak, Alex ; Bernheim, Joelle ; Konikoff, Fred M ; Gilat, Tuvia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3291-2c25582f2c0a014f44fbaf4ec8c2581c1df5a9997e4b6405f6c9300951ba50643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Bile Acids and Salts - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Cholic Acids - therapeutic use</topic><topic>Dietary Fats - administration & dosage</topic><topic>Dietary Fats - adverse effects</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>Fatty Acids - biosynthesis</topic><topic>Fatty Acids - therapeutic use</topic><topic>Fatty Liver - drug therapy</topic><topic>Fatty Liver - etiology</topic><topic>Fatty Liver - metabolism</topic><topic>Fatty Liver - pathology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Lipid Metabolism</topic><topic>Liver - metabolism</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Miscellaneous</topic><topic>Other diseases. Semiology</topic><topic>Other metabolic disorders</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Stearoyl-CoA Desaturase - blood</topic><topic>Weight Gain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leikin-Frenkel, Alicia</creatorcontrib><creatorcontrib>Goldiner, Ilana</creatorcontrib><creatorcontrib>Leikin-Gobbi, Diana</creatorcontrib><creatorcontrib>Rosenberg, Ruth</creatorcontrib><creatorcontrib>Bonen, Hamutal</creatorcontrib><creatorcontrib>Litvak, Alex</creatorcontrib><creatorcontrib>Bernheim, Joelle</creatorcontrib><creatorcontrib>Konikoff, Fred M</creatorcontrib><creatorcontrib>Gilat, Tuvia</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of gastroenterology & hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leikin-Frenkel, Alicia</au><au>Goldiner, Ilana</au><au>Leikin-Gobbi, Diana</au><au>Rosenberg, Ruth</au><au>Bonen, Hamutal</au><au>Litvak, Alex</au><au>Bernheim, Joelle</au><au>Konikoff, Fred M</au><au>Gilat, Tuvia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of preestablished diet-induced fatty liver by oral fatty acid–bile acid conjugates in rodents</atitle><jtitle>European journal of gastroenterology & hepatology</jtitle><addtitle>Eur J Gastroenterol Hepatol</addtitle><date>2008-12</date><risdate>2008</risdate><volume>20</volume><issue>12</issue><spage>1205</spage><epage>1213</epage><pages>1205-1213</pages><issn>0954-691X</issn><eissn>1473-5687</eissn><abstract>BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid–bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents.
AIMThis study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD.
METHODSNAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids.
RESULTSFABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P<0.03). Diglycerides (P<0.003) and triglycerides (P<0.01) were the main neutral liver lipids that decreased during FABAC therapy. Both FABACs tested reduced liver fat in NAFLD at doses of 25 and 150 mg/kg/day. High-fat diet increased, whereas FABAC therapy decreased plasma 16 : 1/(16 : 0+16 : 1) fatty acid ratio – a marker of stearoyl CoA desaturase activity. In HepG2 cells FABACs decreased de-novo fatty acid synthesis dose dependently.
CONCLUSIONOral FABAC therapy decreased liver fat in preestablished NAFLD in mice and rats. Inhibition of stearoyl CoA desaturase activity and fatty acid synthesis are mechanisms that may contribute to this decrease. FABACs may be potential therapeutic agents for human NAFLD.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>18989145</pmid><doi>10.1097/MEG.0b013e3282fc9743</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Bile Acids and Salts - therapeutic use Biological and medical sciences Blood Glucose - metabolism Cholic Acids - therapeutic use Dietary Fats - administration & dosage Dietary Fats - adverse effects Disease Models, Animal Drug Evaluation, Preclinical Fatty Acids - biosynthesis Fatty Acids - therapeutic use Fatty Liver - drug therapy Fatty Liver - etiology Fatty Liver - metabolism Fatty Liver - pathology Gastroenterology. Liver. Pancreas. Abdomen Lipid Metabolism Liver - metabolism Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Metabolic diseases Mice Mice, Inbred BALB C Mice, Inbred C57BL Miscellaneous Other diseases. Semiology Other metabolic disorders Rats Rats, Inbred F344 Stearoyl-CoA Desaturase - blood Weight Gain |
| title | Treatment of preestablished diet-induced fatty liver by oral fatty acid–bile acid conjugates in rodents |
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