Time-dependent network analysis reveals molecular targets underlying the development of diet-induced obesity and non-alcoholic steatohepatitis

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dc.contributor.authorHea-Young Oh-
dc.contributor.authorS K Shin-
dc.contributor.authorH S Heo-
dc.contributor.authorJ S Ahn-
dc.contributor.authorE Y Kwon-
dc.contributor.authorJ H Y Park-
dc.contributor.authorY Y Cho-
dc.contributor.authorH J Park-
dc.contributor.authorM K Lee-
dc.contributor.authorE J Kim-
dc.contributor.authorE J Jung-
dc.contributor.authorR A McGregor-
dc.contributor.authorCheol-Goo Hur-
dc.contributor.authorM S Choi-
dc.date.accessioned2017-04-19T09:40:20Z-
dc.date.available2017-04-19T09:40:20Z-
dc.date.issued2013-
dc.identifier.issn1555-8932-
dc.identifier.uri10.1007/s12263-012-0322-6ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11364-
dc.description.abstractProlonged high-fat diet leads to the development of obesity and multiple comorbidities including non-alcoholic steatohepatitis (NASH), but the underlying molecular basis is not fully understood. We combine molecular networks and time course gene expression profiles to reveal the dynamic changes in molecular networks underlying diet-induced obesity and NASH. We also identify hub genes associated with the development of NASH. Core diet-induced obesity networks were constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet responsive genes identified in liver by time course microarray analysis (8 time points over 24 weeks) of high-fat diet-fed mice compared to normal diet-fed mice. IPA identified five core diet-induced obesity networks with time-dependent gene expression changes in liver. These networks were associated with cell-to-cell signaling and interaction (Network 1), lipid metabolism (Network 2), hepatic system disease (Network 3 and 5), and inflammatory response (Network 4). When we merged these core diet-induced obesity networks, Tlr2, Cd14, and Ccnd1 emerged as hub genes associated with both liver steatosis and inflammation and were altered in a time-dependent manner. Further, protein-protein interaction network analysis revealed Tlr2, Cd14, and Ccnd1 were interrelated through the ErbB/insulin signaling pathway. Dynamic changes occur in molecular networks underlying diet-induced obesity. Tlr2, Cd14, and Ccnd1 appear to be hub genes integrating molecular interactions associated with the development of NASH. Therapeutics targeting hub genes and core diet-induced obesity networks may help ameliorate diet-induced obesity and NASH.-
dc.publisherSpringer-BMC-
dc.titleTime-dependent network analysis reveals molecular targets underlying the development of diet-induced obesity and non-alcoholic steatohepatitis-
dc.title.alternativeTime-dependent network analysis reveals molecular targets underlying the development of diet-induced obesity and non-alcoholic steatohepatitis-
dc.typeArticle-
dc.citation.titleGenes and Nutrition-
dc.citation.number3-
dc.citation.endPage316-
dc.citation.startPage301-
dc.citation.volume8-
dc.contributor.affiliatedAuthorHea-Young Oh-
dc.contributor.affiliatedAuthorCheol-Goo Hur-
dc.contributor.alternativeName오혜영-
dc.contributor.alternativeName신수경-
dc.contributor.alternativeName허형삼-
dc.contributor.alternativeName안지숙-
dc.contributor.alternativeName권은영-
dc.contributor.alternativeName박정한-
dc.contributor.alternativeName조윤영-
dc.contributor.alternativeName박해진-
dc.contributor.alternativeName이미경-
dc.contributor.alternativeName김은정-
dc.contributor.alternativeName정은주-
dc.contributor.alternativeNameMcGregor-
dc.contributor.alternativeName허철구-
dc.contributor.alternativeName최명숙-
dc.identifier.bibliographicCitationGenes and Nutrition, vol. 8, no. 3, pp. 301-316-
dc.identifier.doi10.1007/s12263-012-0322-6-
dc.subject.keywordCirrhosis-
dc.subject.keywordHepatic steatosis-
dc.subject.keywordMicroarray-
dc.subject.keywordNetwork-
dc.subject.keywordObesity-
dc.subject.keywordTranscription-
dc.subject.localCirrhosis-
dc.subject.localHepatic steatosis-
dc.subject.localhepatic steatosis-
dc.subject.localmicroarray-
dc.subject.localmicroarry-
dc.subject.localMicroarray-
dc.subject.localmicroarrays-
dc.subject.localNetwork-
dc.subject.localnetwork-
dc.subject.localObesity-
dc.subject.localobesity-
dc.subject.localTranscription-
dc.subject.localtranscription-
dc.description.journalClassY-
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