Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia.
Details
Serval ID
serval:BIB_6BF81573AFFB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia.
Journal
Cell Metabolism
ISSN
1932-7420 (Electronic)
ISSN-L
1550-4131
Publication state
Published
Issued date
2011
Volume
13
Number
4
Pages
389-400
Language
english
Abstract
The aberrant accumulation of lipids in the liver ("fatty liver") is tightly associated with several components of the metabolic syndrome, including type 2 diabetes, coronary heart disease, and atherosclerosis. Here we show that the impaired hepatic expression of transcriptional cofactor transducin beta-like (TBL) 1 represents a common feature of mono- and multigenic fatty liver mouse models. Indeed, the liver-specific ablation of TBL1 gene expression in healthy mice promoted hypertriglyceridemia and hepatic steatosis under both normal and high-fat dietary conditions. TBL1 deficiency resulted in inhibition of fatty acid oxidation due to impaired functional cooperation with its heterodimerization partner TBL-related (TBLR) 1 and the nuclear receptor peroxisome proliferator-activated receptor (PPAR) α. As TBL1 expression levels were found to also inversely correlate with liver fat content in human patients, the lack of hepatic TBL1/TBLR1 cofactor activity may represent a molecular rationale for hepatic steatosis in subjects with obesity and the metabolic syndrome.
Keywords
Animals, Dietary Fats/pharmacology, Dimerization, Disease Models, Animal, Fatty Liver/etiology, Humans, Hypertriglyceridemia/etiology, Lipid Metabolism/physiology, Liver/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Mice, Transgenic, Nuclear Proteins/metabolism, PPAR alpha/metabolism, RNA Interference, RNA, Small Interfering/metabolism, Receptors, Cytoplasmic and Nuclear/metabolism, Repressor Proteins/metabolism, Transducin/antagonists & inhibitors, Transducin/genetics
Pubmed
Web of science
Open Access
Yes
Create date
11/04/2011 8:11
Last modification date
20/08/2019 15:26