title: Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice.
abstract: OBJECTIVE
  Excessive trans-fatty acids (TFA) consumption has been thought to be a risk factor mainly for coronary artery diseases while less attention has been paid to liver disease. We aimed to clarify the impact of TFA-rich oil consumption on the hepatic pathophysiology compared to natural oil.
  
  
  METHODS
  Mice were fed either a low-fat (LF) or high-fat (HF) diet made of either natural oil as control (LF-C or HF-C) or partially hydrogenated oil, TFA-rich oil (LF-T or HF-T) for 24 weeks. We evaluated the liver and body weight, serological features, liver lipid content and composition, liver histology and hepatic lipid metabolism-related gene expression profile. In addition, primary cultures of mice Kupffer cells (KCs) were evaluated for cytokine secretion and phagocytotic ability after incubation in cis- or trans-fatty acid-containing medium.
  
  
  RESULTS
  The HF-T-fed mice showed significant increases of the liver and body weights, plasma alanine-aminotransferase, free fatty acid and hepatic triglyceride content compared to the HF-C group, whereas the LF-T group did not differ from the LF-C group. HF-T-fed mice developed severe steatosis, along with increased lipogenic gene expression and hepatic TFA accumulation. KCs showed increased tumor necrosis factor secretion and attenuated phagocytotic ability in the TFA-containing medium compared to its cis-isomer.
  
  
  CONCLUSIONS
  Excessive consumption of the TFA-rich oil up-regulated the lipogenic gene expression along with marked hepatic lipid accumulation. TFA might be pathogenic through causing severe steatosis and modulating the function of KCs. The quantity and composition of dietary lipids could be responsible for the pathogenesis of non-alcoholic steatohepatitis.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Obara
authors.forename: Koji
authors.initials: K
authors.lastname: Fukushima
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Yuta
authors.initials: Y
authors.lastname: Wakui
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamai
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ogawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Sato
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsuduki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044242:Trans Fatty Acids / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054392:Adipokines; D016207:Cytokines; D004041:Dietary Fats; D044242:Trans Fatty Acids; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt