Upregulated absorption of dietary palmitic acids with changes in intestinal transporters in non-alcoholic steatohepatitis (NASH)

• Published in: Journal of gastroenterology Vol. 52; no. 8; pp. 940 - 954
• Main Authors: Utsunomiya, Hiroki, Yamamoto, Yasunori, Takeshita, Eiji, Tokumoto, Yoshio, Tada, Fujimasa, Miyake, Teruki, Hirooka, Masashi, Abe, Masanori, Kumagi, Teru, Matsuura, Bunzo, Ikeda, Yoshio, Hiasa, Yoichi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.08.2017; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Apolipoprotein B; Apolipoprotein B-48 - blood; Apolipoprotein B-48 - genetics; Apolipoprotein B-48 - metabolism; Apolipoproteins; Apolipoproteins A - genetics; Apolipoproteins A - metabolism; Biliary Tract; Breath Tests; Carbon Radioisotopes; Carrier Proteins - genetics; Carrier Proteins - metabolism; Case-Control Studies; Caveolin 1 - genetics; CD36 Antigens - genetics; CD36 Antigens - metabolism; Chylomicrons; Chylomicrons - metabolism; Colorectal Surgery; Duodenum; Endoribonucleases - genetics; Endoscopy; Excretion; Fatty Acid Transport Proteins - genetics; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Fatty liver; Female; Fibrosis; Gastroenterology; Glucagon-Like Peptides - blood; Hepatology; Humans; Insulin; Insulin Resistance; Intestinal Absorption; Intestine; Jejunum - metabolism; Liver; Liver Cirrhosis - diagnostic imaging; Liver Cirrhosis - pathology; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Middle Aged; Monomeric GTP-Binding Proteins - genetics; Monomeric GTP-Binding Proteins - metabolism; mRNA; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - pathology; Non-alcoholic Fatty Liver Disease - physiopathology; Original Article—Liver; Palmitic acid; Palmitic Acids - metabolism; Pancreas; Pathogenesis; Protein-Serine-Threonine Kinases - genetics; RNA, Messenger - metabolism; Saturated fatty acids; Steatosis; Surgical Oncology; Triglycerides; Chylomicron; CD36; Non-alcoholic fatty liver disease; Saturated fatty acids; MTTP
• ISSN: 0944-1174; 1435-5922; 1435-5922
• DOI: 10.1007/s00535-016-1298-6

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)]. 13 C-labeled palmitate was administered directly into the duodenum of all participants by gastrointestinal endoscopy. Breath 13 CO 2 levels 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 breath 13 CO 2 levels with hepatic steatosis, fibrosis and insulin resistance was evaluated using laboratory data, elastography results and liver histology findings. Results Overall, 13 CO 2 excretion 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. The 13 CO 2 excretion 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.