Tis7 deletion reduces survival and induces intestinal anastomotic inflammation and obstruction in high-fat diet-fed mice with short bowel syndrome.

Amy M Garcia, Derek Wakeman, Jianyun Lu, Christopher Rowley, Taylor Geisman, Catherine Butler, Shashi Bala, Elzbieta A Swietlicki, Brad W Warner, Marc S Levin, Deborah C Rubin

American journal of physiology. Gastrointestinal and liver physiology 2014 Sep 15

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Effective therapies are limited for patients with parenteral nutrition-dependent short bowel syndrome. We previously showed that intestinal expression of the transcriptional coregulator tetradecanoyl phorbol acetate-induced sequence 7 (tis7) is markedly increased during the adaptive response following massive small bowel resection and tis7 plays a role in normal gut lipid metabolism. Here, we further explore the functional implications of tis7 deletion in intestinal lipid metabolism and the adaptive response following small bowel resection. Intestinal tis7 transgenic (tis7(tg)), tis7(-/-), and wild-type (WT) littermates were subjected to 50% small bowel resection. Mice were fed a control or a high-saturated-fat (42% energy) diet for 21 days. Survival, body weight recovery, lipid absorption, mucosal lipid analysis, and the morphometric adaptive response were analyzed. Quantitative real-time PCR was performed to identify tis7 downstream gene targets. Postresection survival was markedly reduced in high-fat, but not control, diet-fed tis7(-/-) mice. Decreased survival was associated with anastomotic inflammation and intestinal obstruction postresection. High-fat, but not control, diet-fed tis7(-/-) mice had increased intestinal IL-6 expression. Intestinal lipid trafficking was altered in tis7(-/-) compared with WT mice postresection. In contrast, high-fat diet-fed tis7(tg) mice had improved survival postresection compared with WT littermates. High-fat diet feeding in the setting of tis7 deletion resulted in postresection anastomotic inflammation and small bowel obstruction. Tolerance of a calorie-rich, high-fat diet postresection may require tis7 and its target genes. The presence of luminal fat in the setting of tis7 deletion promotes an intestinal inflammatory response postresection.

Citation

Amy M Garcia, Derek Wakeman, Jianyun Lu, Christopher Rowley, Taylor Geisman, Catherine Butler, Shashi Bala, Elzbieta A Swietlicki, Brad W Warner, Marc S Levin, Deborah C Rubin. Tis7 deletion reduces survival and induces intestinal anastomotic inflammation and obstruction in high-fat diet-fed mice with short bowel syndrome. American journal of physiology. Gastrointestinal and liver physiology. 2014 Sep 15;307(6):G642-54