Journal
JOURNAL OF LIPID RESEARCH
Volume 55, Issue 4, Pages 709-717Publisher
ELSEVIER
DOI: 10.1194/jlr.M045922
Keywords
hepatocyte nuclear factor 1 alpha and 4 alpha; liver; human; triglyceride
Categories
Funding
- Swedish Research Council
- Swedish Medical Association
- Swedish Heart-Lung Foundation
- Albert and Gerda Svensson Foundation
- Swedish Diabetes Foundation
- Novo Nordisk Research Foundation
- Stockholm City Council
- Karolinska Institutet
- American Heart Association Grant [09GRNT2060150]
- Natural Science Foundation of China Grant [81070367]
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Acat2 [gene name: sterol O-acyltransferase 2 (SOAT2)] esterifies cholesterol in enterocytes and hepatocytes. This study aims to identify repressor elements in the human SOAT2 promoter and evaluate their in vivo relevance. We identified TG-interacting factor 1 (Tgif1) to function as an important repressor of SOAT2. Tgif1 could also block the induction of the SOAT2 promoter activity by hepatocyte nuclear factor 1 alpha and 4 alpha. Women have similar to 30% higher hepatic TGIF1 mRNA compared with men. Depletion of Tgif1 in mice increased the hepatic Soat2 expression and resulted in higher hepatic lipid accumulation and plasma cholesterol levels. Tgif1 is a new player in human cholesterol metabolism.
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