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Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia

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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 b...

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Main Authors: Kulozik, Philipp (Author) , Jones, Allan (Author) , Mattijssen, Frits (Author) , Rose, Adam J. (Author) , Reimann, Anja (Author) , Strzoda, Daniela (Author) , Kleinsorg, Stefan (Author) , Raupp, Christina (Author) , Kleinschmidt, Jürgen (Author) , Müller-Decker, Karin (Author) , Wahli, Walter (Author) , Sticht, Carsten (Author) , Gretz, Norbert (Author) , von Loeffelholz, Christian (Author) , Stockmann, Martin (Author) , Pfeiffer, Andreas (Author) , Stöhr, Sigrid (Author) , Dallinga-Thie, Geesje M. (Author) , Nawroth, Peter Paul (Author) , Berriel Diaz, Mauricio (Author) , Herzig, Stephan (Author)
Format: Article (Journal)
Language:English
Published: 5 April 2011
In: Cell metabolism
Year: 2011, Volume: 13, Issue: 4, Pages: 389-400
ISSN:1932-7420
DOI:10.1016/j.cmet.2011.02.011
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cmet.2011.02.011
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1550413111000842
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Author Notes:Philipp Kulozik, Allan Jones, Frits Mattijssen, Adam J. Rose, Anja Reimann, Daniela Strzoda, Stefan Kleinsorg, Christina Raupp, Jürgen Kleinschmidt, Karin Müller-Decker, Walter Wahli, Carsten Sticht, Norbert Gretz, Christian von Loeffelholz, Martin Stockmann, Andreas Pfeiffer, Sigrid Stöhr, Geesje M. Dallinga-Thie, Peter P. Nawroth, Mauricio Berriel Diaz, and Stephan Herzig
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Summary: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.
Item Description:Gesehen am 11.07.2022
Physical Description:Online Resource
ISSN:1932-7420
DOI:10.1016/j.cmet.2011.02.011

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