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The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice
Author(s) -
Myronovych Andriy,
SalazarGonzalez RosaMaria,
Ryan Karen K.,
Miles Lili,
Zhang Wujuan,
Jha Pinky,
Wang Li,
Setchell Kenneth D. R.,
Seeley Randy J.,
Kohli Rohit
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20890
Subject(s) - sleeve gastrectomy , nonalcoholic fatty liver disease , medicine , fatty liver , gastroenterology , disease , obesity , weight loss , gastric bypass
Objective Bile acids (BA) are elevated after vertical sleeve gastrectomy (VSG) and farnesoid‐X‐receptor (FXR) is critical to the success of murine VSG. BA downregulate hepatic lipogenesis by activating the FXR‐small heterodimer partner (SHP) pathway. The role of SHP in fatty liver disease improvement after VSG was tested. Methods 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 and composition, steatosis, and BA metabolism gene expression were evaluated. Results 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. Conclusions VSG produces weight loss independent of SHP status. SHP ablation creates a proinflammatory phenotype which is exacerbated after VSG despite weight loss. These inflammatory alterations are possibly related to factors extrinsic to a direct manifestation of NASH.