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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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. Breath 13CO2 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 13CO2 levels with hepatic steatosis, fibrosis and insulin resistance was evaluated using laboratory data, elastography results and liver histology findings.

Results

Overall, 13CO2 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 13CO2 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.

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Acknowledgements

Hiroki Utsunomiya, Yasunori Yamamoto and Yoichi Hiasa designed the experiments; Hiroki Utsunomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda and Yoichi Hiasa conducted experiments and analyzed data; Hiroki Utsunomiya, Yasunori Yamamoto and Yoichi Hiasa performed statistical analyses and wrote the manuscript. All authors revised the manuscript for important intellectual content. Yoichi Hiasa had primary responsibility for the final content. All authors read and approved the final manuscript. Hiroki Utsunomiya, Yasunori Yamamoto, Eiji Takeshita and Yoichi Hiasa obtained funding. This work was supported by a Grant-in-Aid for Scientific Research (JSPS KAKENHI 15K19335 to Yasunori Yamamoto, 15K09008 to Eiji Takeshita, and 15K09006 to Yoichi Hiasa) and by the Program for Enhancing Systematic Education in Graduate School from the Japanese Ministry of Education, Culture, Sports, Science and Technology (to Hiroki Utsunomiya), and from a Grant-in-Aid for Scientific Research and Development from the Japanese Ministry of Health, Labor and Welfare (to Yoichi Hiasa). The authors would like to thank Ms. Takana Fujino, Mr. Kenji Tanimoto, and Ms. Ayumi Sumisaki for their technical assistance.

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  1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan

    Hiroki Utsunomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Tokumoto, Fujimasa Tada, Teruki Miyake, Masashi Hirooka, Masanori Abe, Teru Kumagi, Bunzo Matsuura, Yoshio Ikeda & Yoichi Hiasa

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  1. Hiroki Utsunomiya
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Correspondence to Yoichi Hiasa.

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Utsunomiya, H., Yamamoto, Y., Takeshita, E. et al. Upregulated absorption of dietary palmitic acids with changes in intestinal transporters in non-alcoholic steatohepatitis (NASH). J Gastroenterol 52, 940–954 (2017). https://doi.org/10.1007/s00535-016-1298-6

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