Study of the nuclear receptors involved in fatty livers; establishment of a new pathological model and development of therapeutic application.

肝脏特异性hnf4 α-缺失小鼠（KO小鼠）的触觉PPARα缺失改善了脂肪肝。为探讨脂肪肝的发病机制，分析了触觉PPARα的DNA结合活性。结果，KO小鼠肝脏PPARα的DNA结合活性降低。KO小鼠肝脏ppar γ - 1和PGC1α的表达也增加，肝脏PPARα靶基因被激活。这些结果表明，肝脏PPARγ1、PGC1α和未知的PPARα /γ1配体可以反激活PPARα靶基因，诱导KO小鼠的脂肪生活。

Deletion of haptic PPARα in liver-specific HNF4α-null mice (KO mice) improved fatty livers. To investigate the pathogenic mechanism of fatty livers, DNA binding activity of haptic PPARα was analysed. As a result, DNA binding activity of hepatic PPARα was decreased in KO mice. Expression of hepatic PPARγ1 and PGC1α was also increased and transactivation of hepatic PPARα target genes was observed in KO mice. These results indicate that hepatic PPARγ1, PGC1α, and unidentified ligands for PPARα /γ1 could transactivate the PPARαtarget genes and induce fatty lives in KO mice.