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

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• 作者：Hea-Young Oh (1)
  Su-kyung Shin (2)
  Hyoung-Sam Heo (1)
  Ji-Sook Ahn (1) (6)
  Eun-Young Kwon (2)
  Jung Han Yoon Park (3)
  Yun-young Cho (2)
  Hae-Jin Park (2)
  Mi-Kyung Lee (4)
  Eun Jung Kim (5)
  Un-Ju Jung (2)
  Robin A. McGregor (2)
  Cheol-Goo Hur (1)
  Myung-Sook Choi (2)
  
• 关键词：Transcription ; Cirrhosis ; Hepatic steatosis ; Microarray ; Network ; Obesity
• 刊名：Genes & Nutrition
• 出版年：2013
• 出版时间：May 2013
• 年：2013
• 卷：8
• 期：3
• 页码：301-316
• 全文大小：3850KB
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• 作者单位：Hea-Young Oh (1)
  Su-kyung Shin (2)
  Hyoung-Sam Heo (1)
  Ji-Sook Ahn (1) (6)
  Eun-Young Kwon (2)
  Jung Han Yoon Park (3)
  Yun-young Cho (2)
  Hae-Jin Park (2)
  Mi-Kyung Lee (4)
  Eun Jung Kim (5)
  Un-Ju Jung (2)
  Robin A. McGregor (2)
  Cheol-Goo Hur (1)
  Myung-Sook Choi (2)
  
  1. Division of Biosystems Research, Green Bio Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon, 305-806, Republic of Korea
  2. Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701, Republic of Korea
  6. Department of Bioinformatics, University of Science and Technology (UST), Daejeon, Republic of Korea
  3. Department of Food Science and Nutrition, College of Natural Sciences, Hallym University, Chuncheon, 200-702, Republic of Korea
  4. Department of Food Science and Nutrition, Sunchon National University, Sunchon, Republic of Korea
  5. Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, Republic of Korea
  
• ISSN：1865-3499

文摘

Prolonged 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.