title: Tis7 deletion reduces survival and induces intestinal anastomotic inflammation and obstruction in high-fat diet-fed mice with short bowel syndrome.
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.
authors: Division of Pediatric Gastroenterology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri;
authors: Amy M
authors: AM
authors: Garcia
authors: Department of Pediatric Surgery, Washington University School of Medicine, St. Louis, Missouri;
authors: Derek
authors: D
authors: Wakeman
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors: Jianyun
authors: J
authors: Lu
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors: Christopher
authors: C
authors: Rowley
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors: Taylor
authors: T
authors: Geisman
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors: Catherine
authors: C
authors: Butler
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors: Shashi
authors: S
authors: Bala
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors: Elzbieta A
authors: EA
authors: Swietlicki
authors: Department of Pediatric Surgery, Washington University School of Medicine, St. Louis, Missouri;
authors: Brad W
authors: BW
authors: Warner
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; Department of Medicine, Veterans Affairs St. Louis Health Care System; St. Louis, Missouri; and.
authors: Marc S
authors: MS
authors: Levin
authors: Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri drubin@dom.wustl.edu.
authors: Deborah C
authors: DC
authors: Rubin
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004751:Enteritis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000172:deficiency* / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D007408:Intestinal Absorption; D007415:Intestinal Obstruction / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000601:surgery; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012778:Short Bowel Syndrome / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: C508600:IL6 protein, human; C490044:Ifrd1 protein, mouse; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D008565:Membrane Proteins
keywords: gut inflammation; intestinal adaptation; lipid metabolism; short bowel syndrome