Fig. 4: MitoTam is superior to tamoxifen in improvement of diabetic parametpers.

HFD-fed C57BL/6 mice were divided into three groups: HFD + CO (corn oil); HFD + MT (MitoTam); HFD + TX (tamoxifen); the animals were treated with MitoTam or tamoxifen (2 mg/kg body weight) dissolved in 4% ethanol in corn oil or the vehicle given i.p. twice per week for a period of 4 weeks. a Total body weight was taken once per week (HFD + CO, HFD + TX n = 7; HFD + MT n = 8; 4th week: HFD + CO vs. HFD + MT p = 0.019); Δ body weight was calculated as difference between the initial and final body weight (HFD + CO, HFD + TX n = 7; HFD + MT n = 8; HFD + CO vs. HFD + MT p < 0.001, HFD + CO vs. HFD + TX p < 0.001). b Visceral adipose tissue (VAT) weight was taken at the end of the experiment (n = 6; HFD + CO vs. HFD + MT p < 0.001, HFD + CO vs. HFD + TX p = 0.003). c FI expressed in kcal/day per mouse (HFD + CO, HFD + TX n = 7; HFD + MT n = 8; 2nd week: HFD + CO vs. HFD + MT p = 0.037; 3rd week: HFD + CO vs. HFD + TX p = 0.0033). d Fasting blood glucose at the beginning and end of the experiment was evaluated after 16 h of fasting (HFD + CO, HFD + TX n = 7; HFD + MT n = 8; after treatment HFD + CO vs. HFD + MT p < 0.001) and area under the oGTT curve (AUC) were estimated (HFD + CO, HFD + TX n = 7; HFD + MT n = 8; HFD + CO vs. HFD + MT p < 0.001, HFD + CO vs. HFD + TX p < 0.001, HFD + MT vs. HFD + TX p = 0.029). e Postprandial serum insulin and gastric inhibitory polypeptide (GIP) concentrations were assessed (insulin: HFD + CO, HFD + TX n = 7; HFD + MT n = 8; HFD + CO vs. HFD + MT p = 0.002, HFD + TX vs. HFD + MT p = 0.005; GIP: HFD + CO n = 6, HFD + MT n = 7, HFD + TX n = 6; HFD + CO vs. HFD + MT p = 0.029). f Postprandial serum leptin protein and mRNA in epididymal adipose tissue (EAT) were evaluated (HFD + CO, HFD + TX n = 7; HFD + MT n = 8; serum leptin: HFD + CO vs. HFD + MT p < 0.001, HFD + CO vs. HFD + TX p = 0.014, HFD + TX vs. HFD + MT p < 0.001; leptin mRNA: HFD + CO vs. HFD + MT p = 0.0043, HFD + MT vs. HFD + TX p = 0.0321). g % of SA-β-gal-positive tissue in EAT is shown as bar graph (left), and representative tissue is presented (right; blue color) (n = 6; HFD + TX vs. HFD + MT p = 0.010); p16 ^Ink4a mRNA levels in EAT were assessed by qRT-PCR (n = 6). h, i Oil Red O staining was used for lipid accumulation (averages from 4 independent measurements of three samples; HFD + CO vs. HFD + MT p < 0.001, HFD + TX vs. HFD + MT p < 0.001). j, k Histology of liver sections is shown by H&E staining. For a (∆ B.W.), b, d–g One-Way ANOVA, Tukey´s comparison multiple test was used. For a (total B.W.), c Two-Way ANOVA, Tukey´s comparison multiple test was used. All data are expressed as mean ± SEM; *p < 0.033; **p < 0.002; ***p < 0.001. Source data are provided as a Source Data file.