e="fig"}). If reduced SIRT3 activity is actually responsible for the inactivation of SOD2, we expected these changes to be paralleled by an increase in renal oxidative stress in diabetic mice. Indeed, immunohistochemical analysis showed that nitrotyrosine staining -- a marker of peroxynitrite‐mediated oxidative damage -- was upregulated significantly in the glomerular cells of BTBR *ob/ob* mice compared to those of WT mice (Fig. [1c](#Fig1){ref-type="fig"}).Figure 1Reduction of renal expression and activity of *Sirt3* paralleled with an increase of ROS production in diabetic mice. (**a**) qRT-PCR analysis of *Sirt3* mRNA levels at 14 weeks of age in kidney of BTBR wild-type (WT) mice (n = 9) and BTBR *ob/ob* mice treated with vehicle (n = 6) or honokiol (n = 9) from 8 weeks of age. (**b**) Representative images and quantification of glomerular acetylated SOD2 staining in BTBR WT mice (n = 9) and in BTBR *ob/ob* mice treated with vehicle (n = 6) or honokiol (n = 9) at 14 weeks of age. Insets show acetylated SOD2 in podocytes of WT and diabetic mice (arrowheads). Scale bars: 20 μm. (**c**) Representative images and quantification of glomerular nitrotyrosine staining in BTBR WT mice (n = 9) and in BTBR *ob/ob* mice treated with vehicle (n = 6) or honokiol (n = 9) at 14 weeks of age. Insets show nitrotyrosine staining in podocytes of WT and diabetic mice (arrowheads). Scale bars: 20 μm. (**d,e**) qRT-PCR analysis of *Sirt1* (**d**), and *Sirt6* (**e**) mRNA levels in kidney of BTBR WT mice (n = 9) and BTBR *ob/ob* mice treated with vehicle (n = 6) or honokiol (n = 9) at 14 weeks of age. Data are mean ± SEM and were analyzed by one-way ANOVA followed by Tukey's multiple comparisons test, \**p* \< 0.05, \*\*\**p* \< 0.001 vs BTBR WT mice; ^\#^*p* \< 0.05, ^\#\#\#^*p* \< 0.001 vs BTBR *ob*/*ob* + vehicle.

At this point we wondered whether the manipulation of the SIRT3 pathway with honokiol could have a renoprotective effect. Treatment with honoki