Tsuchiya Takahiro, Naitoh Takeshi, Nagao Munenori, Tanaka Naoki, Watanabe Kazuhiro, Imoto Hirofumi, Miyachi Tomohiro, Motoi Fuyuhiko, Unno Michiaki
Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Obes Surg. 2018 Jun;28(6):1643-1652. doi: 10.1007/s11695-017-3065-z.
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.
非酒精性脂肪性肝炎（NASH）发病率的不断上升已使其成为肝脏相关死亡率的常见原因；然而，尚未确立有效的治疗方法。据报道，减肥手术可改善代谢合并症，如糖尿病和NASH。尽管其机制尚不清楚，但人们认为胆汁酸（BA）通过其核受体法尼醇X受体（FXR）发出的信号变化会产生各种代谢效应。我们试图研究减肥手术对改善NASH的作用及机制。
给雄性Sprague-Dawley大鼠喂食高脂高果糖饮食，这会导致肥胖、胰岛素抵抗和NASH。对大鼠进行十二指肠空肠旁路术（DJB），这是减肥手术的主要组成部分。研究肝脏病理结果和FXR的mRNA表达水平。测量外周血和门静脉血中的血浆BA水平。
DJB抑制体重增加，改善胰岛素抵抗，并主要在炎症方面改善NASH。血浆BA水平以及肝脏中FXR及其靶转录因子小异二聚体伴侣（SHP）的表达均升高。
DJB对改善NASH有直接作用，并且抗炎作用有可能是其机制的一部分。血浆胆汁酸水平的升高以及随后FXR信号的刺激可能导致了这一现象。
