| First Author | Kulozik P | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 4 | Pages | 389-400 |
| PubMed ID | 21459324 | Mgi Jnum | J:172247 |
| Mgi Id | MGI:5005038 | Doi | 10.1016/j.cmet.2011.02.011 |
| Citation | Kulozik P, et al. (2011) Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia. Cell Metab 13(4):389-400 |
| abstractText | 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) alpha. 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. |
