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.
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.
Authors: Samuel Klein; Bettina Mittendorfer; J Christopher Eagon; Bruce Patterson; Lafaine Grant; Nikki Feirt; Ekihiro Seki; David Brenner; Kevin Korenblat; Jennifer McCrea Journal: Gastroenterology Date: 2006-05 Impact factor: 22.682
Authors: Sunder Mudaliar; Robert R Henry; Arun J Sanyal; Linda Morrow; Hanns-Ulrich Marschall; Mark Kipnes; Luciano Adorini; Cathi I Sciacca; Paul Clopton; Erin Castelloe; Paul Dillon; Mark Pruzanski; David Shapiro Journal: Gastroenterology Date: 2013-05-30 Impact factor: 22.682
Authors: Francesco Rubino; David M Nathan; Robert H Eckel; Philip R Schauer; K George M M Alberti; Paul Z Zimmet; Stefano Del Prato; Linong Ji; Shaukat M Sadikot; William H Herman; Stephanie A Amiel; Lee M Kaplan; Gaspar Taroncher-Oldenburg; David E Cummings Journal: Diabetes Care Date: 2016-06 Impact factor: 19.112