Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice

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Authors: Da Som Lee ; Tae Hyeon An ; Hyunmi Kim ; Eunsun Jung ; Gyeonghun Kim ; Seung Yeon Oh ; Jun Seok Kim ; Hye Jin Chun ; Jaeeun Jung ; Eun-Woo Lee ; Baek-Soo Han ; Dai Hoon Han ; Yong-Ho Lee ; Tae-Su Han ; Keun Hur ; Chul-Ho Lee ; Dae-Soo Kim ; Won Kon Kim ; Jun Won Park ; Seung-Hoi Koo ; Je Kyung Seong ; Sang Chul Lee ; Hail Kim ; Kwang-Hee Bae ; Kyoung-Jin Oh

MeSH: Animals ; Diabetes Mellitus, Type 2* / metabolism ; Diet, High-Fat ; Glucose / metabolism ; Hepatocytes / metabolism ; Lipogenesis / genetics ; Liver / metabolism ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease* / genetics ; Non-alcoholic Fatty Liver Disease* / metabolism ; Transcription Factor 7-Like 2 Protein / genetics ; Transcription Factor 7-Like 2 Protein / metabolism ; Triglycerides / metabolism

Keywords: Carbohydrate ; De novo lipogenesis ; Fatty acid ; Glucose ; Insulin ; Lipogenesis ; NAFLD ; TCF7L2 ; TG accumulation ; Type 2 diabetes

Abstract: Aims/hypothesis: Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development. Methods: Tcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2