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

Am J Physiol Gastrointest Liver Physiol. 2014 Sep 15;307(6):G642-54. doi: 10.1152/ajpgi.00374.2013. Epub 2014 Jul 24.

Abstract

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.

Keywords: gut inflammation; intestinal adaptation; lipid metabolism; short bowel syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anastomosis, Surgical
  • Animals
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Enteritis / etiology*
  • Enteritis / genetics
  • Enteritis / metabolism
  • Gene Expression Regulation
  • Immediate-Early Proteins / deficiency*
  • Immediate-Early Proteins / genetics
  • Interleukin-6 / metabolism
  • Intestinal Absorption
  • Intestinal Obstruction / etiology*
  • Intestinal Obstruction / genetics
  • Intestinal Obstruction / metabolism
  • Intestine, Small / metabolism*
  • Intestine, Small / surgery
  • Lipid Metabolism
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Short Bowel Syndrome / complications*
  • Short Bowel Syndrome / genetics
  • Short Bowel Syndrome / metabolism
  • Time Factors

Substances

  • IL6 protein, human
  • Ifrd1 protein, mouse
  • Immediate-Early Proteins
  • Interleukin-6
  • Membrane Proteins