Mus musculus Transcriptome or Gene expression. Mus musculus

Farnesoid X Receptor (FXR) is predominantly expressed in the liver and small intestines. Using both intestine-specific pharmacologic and genetic tools, we demonstrate that it is the intestinal site that exerts the more potent atheroprotective effects of FXR, whereby ileal FXR activates the expression of Fgf15 and Pla2g4c. We show that combining the products of these genes, FGF15/19 and lysophosphotidylcholine, enhance an LXR-mediated cholesterol efflux transcriptional program in mouse macrophages in vitro and in atherosclerotic murine aortas. Relegated to enacting a different transcriptional program in liver, we establish an alternative means of FXR-dependent hepatocyte-macrophage crosstalk paradigm, mediated through ApoAV. Cumulatively, we demonstrate novel models of tissue-specific FXR-mediated communication with pathogenic macrophages.