title: Hypoadiponectinemia accelerates hepatic tumor formation in a nonalcoholic steatohepatitis mouse model.
abstract: OBJECTIVE
  Adipose tissue produces a number of adipocytokines, including adiponectin, leptin, and tumor necrosis factor-alpha. Obesity, which is associated with low plasma adiponectin levels, is an independent risk factor for various liver diseases including nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the effects of adiponectin on the progression of NASH to cirrhosis and tumor formation using adiponectin-knockout (KO) mice.
  
  
  METHODS
  Using a choline-deficient L-amino acid-defined (CDAA) diet-induced mouse NASH model, liver histology and oxidative stress markers were investigated in KO and wild-type (WT) mice.
  
  
  RESULTS
  Hepatic steatosis was enhanced to a greater extent in KO mice, compared to WT mice after a 1-week CDAA diet. After 24 weeks, 6 out of 14 KO mice developed liver cirrhosis and hepatic tumors, whereas the 15 WT mice showed only simple steatosis. In KO mice, hepatic cytochrome P450 2E1 levels were upregulated, and markers of oxidative stress (thiobarbituric acid reactive substances, 8-hydroxydeoxyguanosine-positive cells) were significantly increased compared with WT mice.
  
  
  CONCLUSIONS
  Our results indicate that lack of adiponectin enhances the progression of hepatic steatosis, fibrosis, and hepatic tumor formation in an animal model of NASH. Hypoadiponectinemia in obesity could be a risk factor for NASH-related hepatic tumor formation.
authors: Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Yoshihiro
authors: Y
authors: Kamada
authors: Hitoshi
authors: H
authors: Matsumoto
authors: Shinji
authors: S
authors: Tamura
authors: Juichi
authors: J
authors: Fukushima
authors: Shinichi
authors: S
authors: Kiso
authors: Koji
authors: K
authors: Fukui
authors: Takumi
authors: T
authors: Igura
authors: Norikazu
authors: N
authors: Maeda
authors: Shinji
authors: S
authors: Kihara
authors: Tohru
authors: T
authors: Funahashi
authors: Yuji
authors: Y
authors: Matsuzawa
authors: Iichiro
authors: I
authors: Shimomura
authors: Norio
authors: N
authors: Hayashi
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics; D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002796:Choline Deficiency; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000150:complications* / Q000473:pathology; D006520:Hepatitis, Animal / Q000150:complications* / Q000473:pathology; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D052242:Adiponectin; D000596:Amino Acids; D015415:Biomarkers; D019392:Cytochrome P-450 CYP2E1