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01-06-2018 | Original Contributions

Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH

Authors: Takahiro Tsuchiya, Takeshi Naitoh, Munenori Nagao, Naoki Tanaka, Kazuhiro Watanabe, Hirofumi Imoto, Tomohiro Miyachi, Fuyuhiko Motoi, Michiaki Unno

Published in: Obesity Surgery | Issue 6/2018

Abstract

Background

The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects. We sought to investigate the effects and mechanisms of bariatric surgery on NASH improvement.

Methods

Male Sprague-Dawley rats were fed by a high-fat and high-fructose diet, which results in obesity, insulin resistance, and NASH. Rats underwent duodenal-jejunal bypass (DJB), which is a main component of bariatric procedures. The liver pathological findings and the expression level of mRNA of FXR were investigated. The plasma BA level was measured in peripheral and portal vein blood.

Results

DJB suppressed weight gain, improved insulin resistance, and ameliorated NASH mainly in a point of inflammation. The plasma BA level along with the expression of FXR and its target transcriptional factor, small heterodimer partner (SHP), in the liver were elevated.

Conclusions

DJB has a direct effect on NASH improvement, and there is a possibility that an anti-inflammatory effect is functioning as a part of the mechanism. The increase of plasma bile acid level followed by the stimulation of FXR signaling may contribute to this phenomenon.

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Title: Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH
Authors: Takahiro Tsuchiya
Takeshi Naitoh
Munenori Nagao
Naoki Tanaka
Kazuhiro Watanabe
Hirofumi Imoto
Tomohiro Miyachi
Fuyuhiko Motoi
Michiaki Unno
Publication date: 01-06-2018
Publisher: Springer US
Published in: Obesity Surgery / Issue 6/2018
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI: https://doi.org/10.1007/s11695-017-3065-z

At a glance: The STEP trials

Springer Medicine

Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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