Hepatic Deficiency in Transcriptional Cofactor TBL1 Promotes Liver Steatosis and Hypertriglyceridemia

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• 作者：Philipp Kulozik¹ ; Allan Jones¹ ; ¹² ; Frits Mattijssen¹ ; ¹² ; Adam  ; J. Rose¹ ; Anja Reimann¹ ; Daniela Strzoda¹ ; Stefan Kleinsorg¹ ; Christina Raupp² ; Jü ; rgen Kleinschmidt² ; Karin Mü ; ller-Decker³ ; Walter Wahli⁴ ; Carsten Sticht⁵ ; Norbert Gretz⁵ ; Christian von  ; Loeffelholz⁶ ; ⁷ ; Martin Stockmann⁸ ; Andreas Pfeiffer⁶ ; ⁷ ; Sigrid Stö ; hr⁹ ; Geesje  ; M. Dallinga-Thie¹⁰ ; Peter  ; P. Nawroth¹¹ ; Mauricio  ; Berriel Diaz¹ ; Stephan Herzig¹ ; ^{s.herzig@dkfz.de}
• 刊名：Cell Metabolism
• 出版年：2011
• 出版时间：6 April 2011
• 年：2011
• 卷：13
• 期：4
• 页码：389-400
• 全文大小：784 K

文摘

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.