Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH
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.
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.
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.
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.
KeywordsNon-alcoholic steatohepatitis Bariatric surgery Metabolic surgery Duodenal-jejunal bypass Bile acids
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.
This study was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (Grant No.: 25462011).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
A Statement of Animal Rights/Ethical Approval
All procedures in this study were approved by the Ethics Committee for Animal Research of Tohoku University.
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