However, several lines of evidence support the indirect regulation of PPL expression through FXR: (i) acute administration of synthetic FXR ligand did not induce Ppl mRNA expression in vivo or in vitro; (ii) the attenuated accumulation of PPL during cholestasis in the liver of Fxr−/− mice appeared to be secondary to fat deposition; and (iii) the proximal promoter region of mouse Ppl gene, that was deduced from the human PPL gene [40], does not contain typical FXRE (data not shown). Here, PPL is linked to cholestasis.