The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice.
The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice.
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DOI：
10.1002/oby.20890
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发表时间：
2014-11
期刊：
影响因子：
6.9
通讯作者：
Kohli, Rohit
中科院分区：
文献类型：
--
作者：
Myronovych, Andriy;Salazar-Gonzalez, Rosa-Maria;Ryan, Karen K.;Miles, Lili;Zhang, Wujuan;Jha, Pinky;Wang, Li;Setchell, Kenneth D. R.;Seeley, Randy J.;Kohli, Rohit
垂直袖状胃切除术（VSG）后胆汁酸（BA）升高，而法尼酯X受体（FXR）对小鼠VSG的成功至关重要。BA通过激活FXR-小异源二聚体伴侣（SHP）途径下调肝脏脂肪生成。我们测试了SHP在VSG后脂肪性肝病（NAFLD）改善中的作用。野生型（WT）、SHP肝脏转基因（SHP-Tg）和SHP敲除（SHP-KO）高脂肪饮食（HFD）喂养的小鼠经历VSG或假手术。评价体重、BA水平和组成、脂肪变性和BA代谢基因表达。VSG后肥胖WT小鼠体重减轻，脂肪变性减轻，血浆丙氨酸转氨酶（ALT）降低，BA吸收回肠面积增加，血清BA升高。VSG后的肥胖SHP-Tg小鼠体重也减轻，脂肪变性减少。然而，SHP-KO小鼠对脂肪变性具有抗性，尽管在HFD上体重增加。进一步接受VSG的SHP-KO小鼠体重减轻，但出现肝脏炎症，ALT升高。VSG产生独立于SHP状态的体重减轻。SHP消融产生了促炎表型，尽管体重减轻，但VSG后该表型加重。这些炎症改变可能与NASH直接表现的外在因素有关。
Bile acids (BA) are elevated after vertical sleeve gastrectomy (VSG) and farnesoid-X-receptor (FXR) is critical to the success of murine VSG. BA down-regulate hepatic lipogenesis by activating the FXR-small heterodimer partner (SHP) pathway. We tested the role of SHP in fatty liver disease (NAFLD) improvement after VSG. Wild type (WT), SHP liver-transgenic (SHP-Tg) and SHP knockout (SHP-KO) high-fat diet (HFD) fed mice underwent either VSG or Sham surgery. Body weight, BA level & composition, steatosis and BA metabolism gene expression were evaluated. Obese WT mice post-VSG lost weight, reduced steatosis, decreased plasma alanine aminotransferase (ALT), had more BA absorptive ileal area, and elevated serum BA. Obese SHP-Tg mice post-VSG also lost weight and had decreased steatosis. SHP-KO mice were however resistant to steatosis despite weight gain on a HFD. Further SHP-KO mice that underwent VSG lost weight but developed hepatic inflammation and had increased ALT. VSG produces weight loss independent of SHP status. SHP ablation creates a pro-inflammatory phenotype which is exacerbated after VSG despite weight loss. These inflammatory alterations are possibly related to factors extrinsic to a direct manifestation of NASH.
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影响因子：
15.9
作者：
Watanabe, M;Houten, SM;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
13.5
作者：
Bechmann, Lars P.;Kocabayoglu, Peri;Canbay, Ali
通讯作者：
Canbay, Ali
DOI：
10.1152/ajpgi.00309.2001
发表时间：
2002-01-01
影响因子：
4.5
作者：
Mottino, AD;Hoffman, T;Vore, M
通讯作者：
Vore, M
影响因子：
15.9
作者：
SCHIFF, ER;SMALL, NC;DIETSCHY, JM
通讯作者：
DIETSCHY, JM
影响因子：
6.9
作者：
Steinert, Robert E.;Peterli, Ralph;Beglinger, Christoph
通讯作者：
Beglinger, Christoph