Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia
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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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
5 April 2011
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| In: |
Cell metabolism
Year: 2011, Jahrgang: 13, Heft: 4, Pages: 389-400 |
| ISSN: | 1932-7420 |
| DOI: | 10.1016/j.cmet.2011.02.011 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia |c 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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| 520 | |a 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. | ||
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