Deletion of Tis7 protects mice from high-fat diet-induced weight gain and blunts the intestinal adaptive response postresection

Cong Yu, Shujun Jiang, Jianyun Lu, Carrie C. Coughlin, Yuan Wang, Elzbieta A. Swietlicki, Lihua Wang, Ilja Vietor, Lukas A. Huber, Domagoj Cikes, Trey Coleman, Yan Xie, Clay F. Semenkovich, Nicholas O. Davidson, Marc S. Levin, Deborah C. Rubin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

After loss of intestinal surface area, the remaining bowel undergoes a morphometric and functional adaptive response. Enterocytic expression of the transcriptional coregulator tetradecanoyl phorbol acetate induced sequence 7 (Tis7) is markedly increased in a murine model of intestinal adaptation. Mice overexpressing Tis7 in intestine have greater triglyceride absorption and weight gain when fed a high-fat diet (42% energy) than their wild-type (WT) littermates fed the same diet. These and other data suggest that Tis7 has a unique role in nutrient absorptive and metabolic adaptation. Herein, male Tis7-/- and WT mice were fed a high-fat diet (42% energy) for 8 wk. Weight was monitored and metabolic analyses and hepatic and intestinal lipid concentrations were compared after 8 wk. Intestinal lipid absorption and metabolism studies and intestinal resection surgeries were performed in separate groups of Tis7-/- and WT mice. At 8 wk, weight gain was less and jejunal mucosal and hepatic triglyceride and cholesterol concentrations were lower in Tis7-/- mice than in the WT controls. Following corn oil gavage, serum cholesterol, triglyceride, and FFA concentrations were lower in the Tis7-/- mice than in the WT mice. Incorporation of oral 3[H] triolein into intestinal mucosal cholesterol ester and FFA was less in Tis7-/- compared with WT mice. Following resection, crypt cell proliferation rates and villus heights were lower in Tis7-/- than in WT mice, indicating a blunted adaptive response. Our results suggest a novel physiologic function for Tis7 in the gut as a global regulator of lipid absorption and metabolism and epithelial cell proliferation.

Original languageEnglish
Pages (from-to)1907-1914
Number of pages8
JournalJournal of Nutrition
Volume140
Issue number11
DOIs
StatePublished - Nov 2010

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