TY - JOUR
T1 - Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia
AU - Kulozik, Philipp
AU - Jones, Allan
AU - Mattijssen, Frits
AU - Rose, Adam J.
AU - Reimann, Anja
AU - Strzoda, Daniela
AU - Kleinsorg, Stefan
AU - Raupp, Christina
AU - Kleinschmidt, Jürgen
AU - Müller-Decker, Karin
AU - Wahli, Walter
AU - Sticht, Carsten
AU - Gretz, Norbert
AU - Von Loeffelholz, Christian
AU - Stockmann, Martin
AU - Pfeiffer, Andreas
AU - Stöhr, Sigrid
AU - Dallinga-Thie, Geesje M.
AU - Nawroth, Peter P.
AU - Diaz, Mauricio Berriel
AU - Herzig, Stephan
PY - 2011/4/6
Y1 - 2011/4/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79953765467&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2011.02.011
DO - 10.1016/j.cmet.2011.02.011
M3 - Article
C2 - 21459324
AN - SCOPUS:79953765467
VL - 13
SP - 389
EP - 400
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 4
ER -