Deletion of Tis7 protects mice from high-fat diet-induced weight gain and blunts the intestinal adaptive response postresection.
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.
Yu
Cong
C
Division of Gastroenterology, Washington University School of Medicine, St Louis, MO 63110, USA.
Jiang
Shujun
S
Lu
Jianyun
J
Coughlin
Carrie C
CC
Wang
Yuan
Y
Swietlicki
Elzbieta A
EA
Wang
Lihua
L
Vietor
Ilja
I
Huber
Lukas A
LA
Cikes
Domagoj
D
Coleman
Trey
T
Xie
Yan
Y
Semenkovich
Clay F
CF
Davidson
Nicholas O
NO
Levin
Marc S
MS
Rubin
Deborah C
DC
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation; D004041:Dietary Fats / Q000009:adverse effects*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics*; D007408:Intestinal Absorption / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000601:surgery; D007422:Intestines / Q000473:pathology / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D012778:Short Bowel Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000235:genetics*
D004041:Dietary Fats; C490044:Ifrd1 protein, mouse; D017874:Immediate-Early Proteins; D008055:Lipids; D008565:Membrane Proteins; D012333:RNA, Messenger; D014280:Triglycerides