TY - JOUR
T1 - Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH
AU - Tsuchiya, Takahiro
AU - Naito, Takeshi
AU - Nagao, Munenori
AU - Tanaka, Naoki
AU - Watanabe, Kazuhiro
AU - Imoto, Hirofumi
AU - Miyachi, Tomohiro
AU - Motoi, Fuyuhiko
AU - Unno, Michiaki
N1 - Funding Information:
Funding Information This study was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (Grant No.: 25462011).
Funding Information:
The authors thank Dr. Fumiyoshi Fujishima for contribution in pathological diagnosis, Ms. Emiko Shibuya for technical assistance, and the staff of Institute for Animal Experimentation, Graduate School of Medicine, Tohoku University, for assistance with animal husbandry and care.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Bariatric surgery
KW - Bile acids
KW - Duodenal-jejunal bypass
KW - Metabolic surgery
KW - Non-alcoholic steatohepatitis
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U2 - 10.1007/s11695-017-3065-z
DO - 10.1007/s11695-017-3065-z
M3 - Article
C2 - 29235014
AN - SCOPUS:85037719258
VL - 28
SP - 1643
EP - 1652
JO - Obesity Surgery
JF - Obesity Surgery
SN - 0960-8923
IS - 6
ER -