Figure 2.A FXR/SIRT1
positive-feedback regulatory loop. The expression and activity of FXR
and SIRT1 are mutually and coordinately regulated. SIRT1 positively
auto-regulates its own expression by inhibiting miR-34a via deacetylation
(as indicated by dotted circles) of p53 and histones at the miR-34a
promoter (short loop) and by increasing transactivation potential of FXR
via deacetylating the FXR (long loop). SIRT1 also increases FXR expression
and activity via deacetylation of PGC-1α.
FXR in turn positively regulates hepatic SIRT1 expression by inhibiting
miR-34a which targets SIRT1.
