Document Detail


Targeted intestinal overexpression of the immediate early gene tis7 in transgenic mice increases triglyceride absorption and adiposity.
MedLine Citation:
PMID:  16085642     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Following loss of functional small bowel surface area due to surgical resection, the remnant gut undergoes an adaptive response characterized by increased crypt cell proliferation and enhanced villus height and crypt depth, resulting in augmented intestinal nutrient absorptive capacity. Previous studies showed that expression of the immediate early gene tis7 is markedly up-regulated in intestinal enterocytes during the adaptive response. To study its role in the enterocyte, transgenic mice were generated that specifically overexpress TIS7 in the gut. Nucleotides -596 to +21 of the rat liver fatty acid-binding protein promoter were used to direct abundant overexpression of TIS7 into small intestinal upper crypt and villus enterocytes. TIS7 transgenic mice had increased total body adiposity and decreased lean muscle mass compared with normal littermates. Oxygen consumption levels, body weight, surface area, and small bowel weight were decreased. On a high fat diet, transgenic mice exhibited a more rapid and proportionately greater gain in body weight with persistently elevated total body adiposity and increased hepatic fat accumulation. Bolus fat feeding resulted in a greater increase in serum triglyceride levels and an accelerated appearance of enterocytic, lamina propria, and hepatic fat. Changes in fat homeostasis were linked to increased expression of genes involved in enterocytic triglyceride metabolism and changes in growth with decreased insulin-like growth factor-1 expression. Thus, TIS7 overexpression in the intestine altered growth, metabolic rate, adiposity, and intestinal triglyceride absorption. These results suggest that TIS7 is a unique mediator of nutrient absorptive and metabolic adaptation following gut resection.
Authors:
Yuan Wang; Hristo Iordanov; Elzbieta A Swietlicki; Lihua Wang; Christine Fritsch; Trey Coleman; Clay F Semenkovich; Marc S Levin; Deborah C Rubin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-08-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-12-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34764-75     Citation Subset:  IM    
Affiliation:
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / metabolism*
Animals
Blotting, Northern
Body Composition
Body Weight
Calorimetry
Cell Proliferation
Enterocytes / cytology,  metabolism
Fatty Acid-Binding Proteins / genetics
Gene Expression Regulation*
Glucose / metabolism
Growth Hormone / blood
Homeostasis
Immediate-Early Proteins / genetics*,  physiology*
Immunoblotting
Immunohistochemistry
Insulin / blood
Insulin-Like Growth Factor I / metabolism
Intestines / metabolism
Leptin / blood
Lipids / chemistry
Liver / metabolism
Membrane Proteins / genetics*,  physiology*
Mice
Mice, Transgenic
Microscopy, Electron
Oxygen Consumption
Promoter Regions, Genetic
Rats
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Triglycerides / chemistry,  metabolism*
Up-Regulation
Grant Support
ID/Acronym/Agency:
AG20091/AG/NIA NIH HHS; DK46122/DK/NIDDK NIH HHS; DK50466/DK/NIDDK NIH HHS; DK52574/DK/NIDDK NIH HHS; DK56341/DK/NIDDK NIH HHS; DK61216/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acid-Binding Proteins; 0/Ifrd1 protein, mouse; 0/Immediate-Early Proteins; 0/Leptin; 0/Lipids; 0/Membrane Proteins; 0/Triglycerides; 11061-68-0/Insulin; 50-99-7/Glucose; 67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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