Research Perspective Volume 2, Issue 8 pp 527—534

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.