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
Author(s)
Kulozik P., Jones A., Mattijssen F., Rose A.J., Reimann A., Strzoda D., Kleinsorg S., Raupp C., Kleinschmidt J., Müller-Decker K., Wahli W., Sticht C., Gretz N., von Loeffelholz C., Stockmann M., Pfeiffer A., Stöhr S., Dallinga-Thie G.M., Nawroth P.P., Berriel Diaz M., Herzig S.
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
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