Premium
Deletion of HNF 1 α in hepatocytes results in fatty liver‐related hepatocellular carcinoma in mice
Author(s) -
Ni Qi,
Ding Kai,
Wang KeQi,
He Jin,
Yin Chuan,
Shi Jian,
Zhang Xin,
Xie WeiFen,
Shi YongQuan
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12689
Subject(s) - hepatocellular carcinoma , hepatocyte , knockout mouse , cirrhosis , hepatocyte nuclear factor 4 , hepatocyte nuclear factors , fatty liver , medicine , endocrinology , hepatocyte growth factor , liver function , lipid metabolism , tumor necrosis factor alpha , cancer research , transcription factor , biology , chemistry , biochemistry , gene , receptor , nuclear receptor , disease , in vitro
Hepatocyte nuclear factor 1α ( HNF 1α) is a liver‐enriched transcription factor that is critical for the maintenance of hepatocyte function. Our previous studies have demonstrated the therapeutic effects of HNF 1α on hepatic fibrosis and hepatocellular carcinoma ( HCC ) in animals. In this study, we created hepatocyte‐specific Hnf1 α knockout mice using the Cre‐ loxP recombination system. The knockout mice display increased fatty acid synthesis in the liver. Moreover, these mice spontaneously develop HCC through fatty liver without cirrhosis. Inflammatory cytokines, such as tumor necrosis factor α and IL ‐6, are upregulated and accompanied by increased phosphorylation of Akt, p‐65 and STAT 3 in the livers of HNF 1α knockout mice. Our findings suggest that HNF 1α plays a crucial role in hepatocyte lipid metabolism and hepatocarcinogenesis.