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

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 mell...

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Bibliographic Details
Published in:Obesity surgery 2018-06, Vol.28 (6), p.1643-1652
Main Authors: Tsuchiya, Takahiro, Naitoh, Takeshi, Nagao, Munenori, Tanaka, Naoki, Watanabe, Kazuhiro, Imoto, Hirofumi, Miyachi, Tomohiro, Motoi, Fuyuhiko, Unno, Michiaki
Format: Article
Language:English
Subjects:
Bile
Gastrointestinal surgery
Insulin resistance
Medicine
Medicine & Public Health
Metabolism
Original Contributions
Rodents
Surgery
Surgical outcomes
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Summary: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.
ISSN:0960-8923
1708-0428
DOI:10.1007/s11695-017-3065-z