title: Upregulated absorption of dietary palmitic acids with changes in intestinal transporters in non-alcoholic steatohepatitis (NASH).
abstract: BACKGROUND
  Palmitic acid is an important risk factor for the pathogenesis of non-alcoholic steatohepatitis (NASH), but changes in palmitic acid intestinal absorption in NASH are unclear. The aim of this study was to clarify changes in palmitic acid intestinal absorption and their association with the pathogenesis of NASH.
  
  
  METHODS
  A total of 106 participants were recruited to the study, of whom 33 were control subjects (control group), 32 were patients with NASH Brunt stage 1-2 [early NASH (e-NASH)], and 41 were patients with NASH Brunt stage 3-4 [advanced NASH (a-NASH)].13C-labeled palmitate was administered directly into the duodenum of all participants by gastrointestinal endoscopy. Breath13CO2levels were measured to quantify palmitic acid absorption, and serum Apolipoprotein B-48 (ApoB-48) concentrations were measured after a test meal to quantify absorbed chylomicrons. Expressions of fatty acid (FA) transporters were also examined. The associations of breath13CO2levels with hepatic steatosis, fibrosis and insulin resistance was evaluated using laboratory data, elastography results and liver histology findings.
  
  
  RESULTS
  Overall,13CO2excretion was significantly higher in e-NASH patients than in the control subjects and a-NASH patients (P < 0.01). e-NASH patients had higher serum ApoB-48 levels, indicating increased palmitic acid transport via chylomicrons in these patients. Jejunal mRNA and protein expressions of microsomal triglyceride transfer protein and cluster of differentiation 36 were also increased in both NASH patient groups. The13CO2excretion of e-NASH patients was significantly correlated with the degree of hepatic steatosis, fibrosis and insulin resistance (P = 0.005, P < 0.001, P = 0.019, respectively).
  
  
  CONCLUSIONS
  Significantly upregulated palmitic acid absorption by activation of its transporters was evident in patients with NASH, and clinical progression of NASH was related to palmitic acid absorption. These dietary changes are associated with the onset and progression of NASH.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Utsunomiya
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Takeshita
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tokumoto
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Fujimasa
authors.initials: F
authors.lastname: Tada
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Teruki
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Hirooka
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Teru
authors.initials: T
authors.lastname: Kumagi
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Bunzo
authors.initials: B
authors.lastname: Matsuura
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. hiasa@m.ehime-u.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
mesh_terms: D000328:Adult; D000368:Aged; D053283:Apolipoprotein B-48 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism; D001944:Breath Tests; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics; D002914:Chylomicrons / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics; D050612:Fatty Acid Transport Proteins / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D004763:Glucagon-Like Peptides / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D010169:Palmitic Acids / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D053283:Apolipoprotein B-48; D001054:Apolipoproteins A; D018955:CD36 Antigens; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D051242:Caveolin 1; D002914:Chylomicrons; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D010169:Palmitic Acids; D012333:RNA, Messenger; C493571:SLC27A4 protein, human; C022205:apolipoprotein A-IV; C106092:microsomal triglyceride transfer protein; D004763:Glucagon-Like Peptides; C403982:ERN2 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: CD36; Chylomicron; MTTP; Non-alcoholic fatty liver disease; Saturated fatty acids