Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis
The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metab...
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| Veröffentlicht in: | PloS one 2012-08, Vol.7 (8), p.e42915-e42915 |
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| creator | Ku, Bon Jeong Kim, Tae Hoon Lee, Jae Hee Buras, Eric D White, Lisa D Stevens, Robert D Ilkayeva, Olga R Bain, James R Newgard, Christopher B DeMayo, Francesco J Jeong, Jae-Wook |
| description | The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+)Mig-6(f/f); Mig-6(d/d)). Mig-6(d/d) mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d) mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d) mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d) mice compared to Mig-6(f/f) controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease. |
| doi_str_mv | 10.1371/journal.pone.0042915 |
| format | Article |
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Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+)Mig-6(f/f); Mig-6(d/d)). Mig-6(d/d) mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d) mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d) mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d) mice compared to Mig-6(f/f) controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0042915</identifier><identifier>PMID: 22912762</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Albumin ; Amino acids ; Analysis ; Animals ; Azo Compounds ; Bile ; Bile acids ; Bile Acids and Salts - analysis ; Bile Acids and Salts - biosynthesis ; Biology ; Blood cholesterol ; Blotting, Western ; Cardiovascular diseases ; Cardiovascular Diseases - etiology ; Chemical synthesis ; Cholesterol ; Cholesterol - blood ; Cholesterol - metabolism ; Deoxycholic acid ; Deoxyribonucleic acid ; DNA ; DNA microarrays ; Excretion ; Fatty liver ; Feces - chemistry ; Gene expression ; Gene Expression Regulation - genetics ; Genes ; High density lipoprotein ; Homeostasis ; Homeostasis - physiology ; Hormones ; House mouse ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Lipid metabolism ; Liver ; Liver - metabolism ; Low density lipoprotein ; Low density lipoproteins ; Medical treatment ; Medicine ; Metabolism ; Mice ; Microarray Analysis ; Mitogens ; Molecular modelling ; mRNA ; Nutrition ; Physiological aspects ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Rodents ; Serum levels</subject><ispartof>PloS one, 2012-08, Vol.7 (8), p.e42915-e42915</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Ku et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Ku et al 2012 Ku et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-f3f5cb5948112dd579c3b72b3da36364467a7648a542822fe82f965c284139df3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422237/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422237/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22912762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lobaccaro, Jean-Marc A.</contributor><creatorcontrib>Ku, Bon Jeong</creatorcontrib><creatorcontrib>Kim, Tae Hoon</creatorcontrib><creatorcontrib>Lee, Jae Hee</creatorcontrib><creatorcontrib>Buras, Eric D</creatorcontrib><creatorcontrib>White, Lisa D</creatorcontrib><creatorcontrib>Stevens, Robert D</creatorcontrib><creatorcontrib>Ilkayeva, Olga R</creatorcontrib><creatorcontrib>Bain, James R</creatorcontrib><creatorcontrib>Newgard, Christopher B</creatorcontrib><creatorcontrib>DeMayo, Francesco J</creatorcontrib><creatorcontrib>Jeong, Jae-Wook</creatorcontrib><title>Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+)Mig-6(f/f); Mig-6(d/d)). Mig-6(d/d) mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d) mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d) mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d) mice compared to Mig-6(f/f) controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.</description><subject>Acids</subject><subject>Albumin</subject><subject>Amino acids</subject><subject>Analysis</subject><subject>Animals</subject><subject>Azo Compounds</subject><subject>Bile</subject><subject>Bile acids</subject><subject>Bile Acids and Salts - analysis</subject><subject>Bile Acids and Salts - biosynthesis</subject><subject>Biology</subject><subject>Blood cholesterol</subject><subject>Blotting, Western</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - etiology</subject><subject>Chemical synthesis</subject><subject>Cholesterol</subject><subject>Cholesterol - blood</subject><subject>Cholesterol - metabolism</subject><subject>Deoxycholic acid</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>Excretion</subject><subject>Fatty liver</subject><subject>Feces - chemistry</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - genetics</subject><subject>Genes</subject><subject>High density lipoprotein</subject><subject>Homeostasis</subject><subject>Homeostasis - physiology</subject><subject>Hormones</subject><subject>House mouse</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Lipid metabolism</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Low density lipoprotein</subject><subject>Low density lipoproteins</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Microarray Analysis</subject><subject>Mitogens</subject><subject>Molecular modelling</subject><subject>mRNA</subject><subject>Nutrition</subject><subject>Physiological aspects</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA</subject><subject>Rodents</subject><subject>Serum 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R</au><au>Newgard, Christopher B</au><au>DeMayo, Francesco J</au><au>Jeong, Jae-Wook</au><au>Lobaccaro, Jean-Marc A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-08-17</date><risdate>2012</risdate><volume>7</volume><issue>8</issue><spage>e42915</spage><epage>e42915</epage><pages>e42915-e42915</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+)Mig-6(f/f); Mig-6(d/d)). Mig-6(d/d) mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d) mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d) mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d) mice compared to Mig-6(f/f) controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22912762</pmid><doi>10.1371/journal.pone.0042915</doi><tpages>e42915</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1326267498 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Albumin Amino acids Analysis Animals Azo Compounds Bile Bile acids Bile Acids and Salts - analysis Bile Acids and Salts - biosynthesis Biology Blood cholesterol Blotting, Western Cardiovascular diseases Cardiovascular Diseases - etiology Chemical synthesis Cholesterol Cholesterol - blood Cholesterol - metabolism Deoxycholic acid Deoxyribonucleic acid DNA DNA microarrays Excretion Fatty liver Feces - chemistry Gene expression Gene Expression Regulation - genetics Genes High density lipoprotein Homeostasis Homeostasis - physiology Hormones House mouse Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Lipid metabolism Liver Liver - metabolism Low density lipoprotein Low density lipoproteins Medical treatment Medicine Metabolism Mice Microarray Analysis Mitogens Molecular modelling mRNA Nutrition Physiological aspects Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA Rodents Serum levels |
| title | Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T07%3A00%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mig-6%20plays%20a%20critical%20role%20in%20the%20regulation%20of%20cholesterol%20homeostasis%20and%20bile%20acid%20synthesis&rft.jtitle=PloS%20one&rft.au=Ku,%20Bon%20Jeong&rft.date=2012-08-17&rft.volume=7&rft.issue=8&rft.spage=e42915&rft.epage=e42915&rft.pages=e42915-e42915&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0042915&rft_dat=%3Cgale_plos_%3EA498260247%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326267498&rft_id=info:pmid/22912762&rft_galeid=A498260247&rft_doaj_id=oai_doaj_org_article_0e6359e405594a9ba2f1da5581cf38fe&rfr_iscdi=true |