ving honokiol (data not shown). To test whether increased *Sirt3* mRNA levels, after honokiol treatment, were associated with its increased activity, we analyzed SOD2 acetylation status also in the tubules. Similar to the glomerular compartment, we observed an increased acetylation of SOD2 in the proximal tubules of BTBR *ob/ob* mice given vehicle, which was reduced in mice after honokiol treatment (*p* \< 0.01 *vs* vehicle, Fig. [5c](#Fig5){ref-type="fig"}). To investigate whether the increased expression and activity of *Sirt3* in tubular cells of honokiol-treated diabetic mice can contribute also to increased SIRT3 activity in the glomerular compartment, as it has been established with regard to SIRT1^[@CR29]^, we evaluated the expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for the biosynthesis of nicotinamide adenine dinucleotide (NAD^+^), the essential co-factor of SIRT3 activity. Our results showed that *Nampt* mRNA expression was significantly lower in the kidneys of BTBR *ob/ob* mice given vehicle than in those of WT mice (*p* \< 0.05), and treatment with honokiol restored *Nampt* levels (*p* \< 0.01 versus vehicle) in the diabetic mice (Fig. [5d](#Fig5){ref-type="fig"}).Figure 5Glomerular SIRT3 activation is associated with enhanced tubular *Sirt3* expression. (**a**,**b**) Representative images (**a**) and quantification (**b**) of *in situ* hybridization for *Sirt3* in kidney cortex from BTBR WT mice and BTBR *ob/ob* mice treated with vehicle or honokiol at 14 weeks of age. Scale bars: 20 μm. Insets show the localization of *Sirt3* in tubular cells. Image-based quantitative software analysis was performed to evaluate tubular expression of *Sirt3*. Fiji Image J software (<https://imagej.net/Fiji>) was used for the quantification of the number of *Sirt3* mRNA dots (representing single mRNA molecules). Orbit Image analysis software (<http://orbit.bio>) was used to count the number of cells. *Sirt3* mRNA levels were expressed as average number of dots 