Hepatic FGF21 is under the Regulation of the Canonical Wnt Signaling Pathway

Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator for its involvement in energy homeostasis and insulin signaling sensitization. Our lab has obtained preliminary observation suggesting that hepatic FGF21 is reduced in male LTCFDN, a transgenic mouse line in which canonical Wnt signaling cascade is functionally attenuated. With approaches including Western blotting, quantitative RT-PCR, and ELISA, I verified reduced hepatic Fgf21 mRNA and FGF21 protein levels, along with reduced fasting plasma FGF21 level in male LTCFDN mice. This reduction was not associated with reduced expression of Pparα, a known Fgf21 transactivator. Utilizing mouse primary hepatocytes, luciferase reporter assay, and chromatin immunoprecipitation, I determined the stimulation of Fgf21 expression by Wnt activation at transcriptional level, attributed to increased TCF7L2 binding to the Fgf21 promoter. My observations collectively suggest that Wnt signaling cascade is involved in hepatic FGF21 production, and this positive regulation is likely independent of PPARα-mediated regulation.M.Sc