Dominant-negative HNF1α mutant promotes liver steatosis and inflammation by regulating hepatic complement factor D. Dominant-negative HNF1α mutant promotes liver steatosis and inflammation by regulating hepatic complement factor D

Heterozygous mutations of HNF1A gene are the pathogenic cause of MODY3. A few studies reported that MODY3 patients may have dyslipidemia and early onset of liver steatosis in some cases. However, there is a lack of sufficient and reliable experimental evidence on how HNF1α regulates NAFLD progression under the genetic background of MODY3. We established a novel mouse model carrying the dominant-negative human HNF1α P291fsinsC mutation (termed as hHNF1Amut/- mice). The hepatic morphological phenotypes and the changes of lipid metabolism were investigated. To reveal the molecular changes, we performed the transcriptome and proteome analysis. Overall design: As the transcriptome and proteome analysis suggested, the expression of complement factor D (CFD), which was reported to promote HFD-induced hepatic steatosis and inflammation, was significantly upregulated. Comparative gene expression profiling analysis of RNA-seq data for hHNF1A-/- and hHNF1Amut/- mice liver (3 Control vs 4 KI).