title: Integrative transcriptomic analysis of NAFLD animal model reveals dysregulated genes and pathways in metabolism.
abstract: Dysregulation of metabolism in hepatocytes leads to hepatic diseases such as hepatitis and non-alcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is likely to progress to cirrhosis, liver failure and hepatocellular carcinoma, which lead to poor long-term prognosis. However, the exact mechanism of development of NAFLD is not well elucidated. In order to better understand the pathogenesis of NAFLD, we have performed an integrative analysis to livers from NAFLD rat models in a global view of the transcriptome. By systemic and integrative analyses, we have found that transport, angiogenesis and cell adhesion were upregulated in response to high fat diet feeding, which may cause a large amount of free fatty acid transport, hepatic fibrosis and hepatocytes injury. GO tree analysis has shown that angiogenesis was upregulated. GO term in response to high fat diet which may cause fibrosis. The pathway interaction network has indicated that upregulated "valine, leucine, and isoleucine metabolism" may decrease the serum concentration of branched-chain amino acid (BCAA). The enhanced degradation of BCAA in NAFLD animal models may lead to inhibition of the regeneration of hepatocytes, reducing the production of albumin, attenuating the inhibition of liver cancer and decreasing immunity. Overall, high fat diet upregulated a variety of metabolism which have converged at TCA cycle. High fatty has pushed the hepatic mitochondria to a "busy state". Comprehensively, genes participated in dysregulated biological process and metabolisms may be served as indicators for evaluation of NAFLD progression and therapeutic targets.
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, People's Republic of China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China. Electronic address: hzl579@163.com.
authors.forename: Zongliu
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Geriatrics, Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China. Electronic address: 13908864176@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002952:Citric Acid Cycle / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome
chemical_list: D000596:Amino Acids
keywords: Animal model; Bioinformatic analysis; Metabolism; Non-alcoholic fatty liver disease; RNA sequencing