The mechanism of increased intestinal palmitic acid absorption and its impact on hepatic stellate cell activation in nonalcoholic steatohepatitis

Masakazu Hanayama,Yoichi Hiasa,Yasunori Yamamoto,Masaki Mogi,Yoshiou Ikeda,Shuang Liu,Hiroki Utsunomiya,Osamu Yoshida,Eiji Takeshita,Bunzo Matsuura

doi:10.1038/s41598-021-92790-z

Masakazu Hanayama, Yoichi Hiasa + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-92790-z

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Journal: Scientific Reports	Publication Date: Jun 28, 2021
Citations: 5	License type: open-access

Affiliation: Ehime University

Abstract

Dietary palmitic acid (PA) promotes liver fibrosis in patients with nonalcoholic steatohepatitis (NASH). Herein, we clarified the intestinal absorption kinetics of dietary PA and effect of trans-portal PA on the activation of hepatic stellate cells (HSCs) involved in liver fibrosis in NASH. Blood PA levels after meals were significantly increased in patients with NASH compared to those in the control. Expression of genes associated with fat absorption and chylomicron formation, such as CD36 and MTP, was significantly increased in the intestine of NASH model rats compared with that in the controls. Plasma levels of glucagon-like peptide-2, involved in the upregulation of CD36 expression, were elevated in NASH rats compared with those in the controls. Furthermore, portal PA levels after meals in NASH rats were significantly higher than those in control and nonalcoholic fatty liver rats. Moreover, PA injection into the portal vein to the liver in control rats increased the mRNA levels associated with the activation of HSCs. Increased intestinal absorption of diet-derived PA was observed in NASH. Thus, the rapid increase in PA levels via the portal vein to the liver may activate HSCs and affect the development of liver fibrosis in NASH.

Highlights

Dietary palmitic acid (PA) promotes liver fibrosis in patients with nonalcoholic steatohepatitis (NASH)
We measured the change in Fatty acids (FAs) levels in the serum before and after meals, which revealed that only saturated fatty acids (SFAs) were significantly increased in patients with NASH compared to those in controls (P < 0.01, Fig. 1A)
This study was designed to evaluate the kinetics of PA absorption in the intestine and to evaluate the effect of PA, administered via the portal vein, on the activation of hepatic stellate cells (HSCs) in pathogenesis of NASH

Summary

Introduction

Dietary palmitic acid (PA) promotes liver fibrosis in patients with nonalcoholic steatohepatitis (NASH). We investigated the mechanism underlying increased intestinal absorption of PA using a rat model of NASH and evaluated the effect of dietary PA administered via the portal vein on the activation of HSCs in NASH. We measured the change in FA levels in the serum before and after meals, which revealed that only saturated fatty acids (SFAs) were significantly increased in patients with NASH compared to those in controls (P < 0.01, Fig. 1A).

Results

Conclusion