vehicle or honokiol at 14 weeks of age. Scale bars: 2 μm. (**b**) Enlarged images show mitochondria structure in podocytes of WT and diabetic mice. Scale bars: 500 nm. (**c**) Representative images and quantification of glomerular PGC-1α expression in BTBR WT mice (n = 9) and in BTBR *ob/ob* mice treated with vehicle (n = 6) and honokiol (n = 9) at 14 weeks of age. Honokiol increases the percentage of PGC-1α-positive nuclei in diabetic mice (arrowheads and insets). Scale bars: 20 μm. Data are mean ± SEM and were analyzed by one-way ANOVA followed by Tukey's multiple comparisons test, \*\*\**p* \< 0.001 vs BTBR WT mice; ^\#\#^*p* \< 0.01 vs BTBR *ob/ob* + vehicle.

To further assess the protective role of honokiol treatment, we investigated the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) -- the master regulator of mitochondrial function^[@CR27],[@CR28]^. We found that PGC-1α was significantly lower in the glomerular cells of diabetic mice (*p* \< 0.001), while its expression was restored to control levels through treatment with honokiol (*p* \< 0.01 versus vehicle, Fig. [4c](#Fig4){ref-type="fig"}).

Honokiol restores tubular expression of Sirt3 {#Sec7}
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The modulation of total *Sirt3* mRNA expression and its upregulation by honokiol in diabetic mice prompted us to assess *Sirt3* mRNA localization in the kidney through *in situ* hybridization experiments. We found that *Sirt3* was predominantly expressed in the tubular compartment of WT mice (Fig. [5a](#Fig5){ref-type="fig"}). In BTBR *ob/ob* mice given vehicle, the tubular expression of *Sirt3* was significantly lower compared with WT mice (*p* \< 0.05), but it was restored (*p* \< 0.01 versus vehicle) through honokiol treatment (Fig. [5a,b](#Fig5){ref-type="fig"}). In contrast, a weak *Sirt3* mRNA signal was found in the glomeruli of WT mice, which was not altered in either diabetic mice given vehicle or in those recei