The Role of HFN1αA98V in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma Development

Abstract

Hepatic Nuclear Factor 1-Alpha (HNF1α) is a transcription factor that plays a critical role in the development and function of several organs. Mutations in HNF1α have been associated with monogenetic diabetes and GI cancer development. An Hnf1α A98V germline mouse model was developed, and mice were put on high fat diets to examine what pathways were affected by the Hnf1α mutations in the context of a high fat diet. Immunofluorescence, RT-qPCR and western blot experiments were conducted on the livers of sacrificed mice. Fabp1 was reduced in high fat diet mice with Hnf1α mutations. Pcsk9 was upregulated in hetero and homozygous mice on a high fat diet, yet Pcsk9 expression was reduced in HCC compared to normal adjacent tissue. Hnf1α plays a role in lipid metabolism and mutations in Hnf1α may exacerbate aberrant lipid storage in the liver and predispose individuals to HCC development.