| First Author | Wu S | Year | 2010 |
| Journal | Hum Mol Genet | Volume | 19 |
| Issue | 4 | Pages | 597-608 |
| PubMed ID | 19995791 | Mgi Jnum | J:155867 |
| Mgi Id | MGI:4417985 | Doi | 10.1093/hmg/ddp526 |
| Citation | Wu S, et al. (2010) Upstream transcription factor 1 influences plasma lipid and metabolic traits in mice. Hum Mol Genet 19(4):597-608 |
| abstractText | Upstream transcription factor 1 (USF1) has been associated with familial combined hyperlipidemia, the metabolic syndrome, and related conditions, but the mechanisms involved are unknown. In this study, we report validation of Usf1 as a causal gene of cholesterol homeostasis, insulin sensitivity and body composition in mouse models using several complementary approaches and identify associated pathways and gene expression network modules. Over-expression of human USF1 in both transgenic mice and mice with transient liver-specific over-expression influenced metabolic trait phenotypes, including obesity, total cholesterol level, LDL/VLDL cholesterol and glucose/insulin ratio. Additional analyses of trait and hepatic gene expression data from an F2 population derived from C57BL/6J and C3H/HeJ strains in which there is a naturally occurring variation in Usf1 expression supported a causal role for Usf1 for relevant metabolic traits. Gene network and pathway analyses of the liver gene expression signatures in the F2 population and the hepatic over-expression model suggested the involvement of Usf1 in immune responses and metabolism, including an Igfbp2-centered module. In all three mouse model settings, notable sex specificity was observed, consistent with human studies showing differences in association with USF1 gene polymorphisms between sexes. |
