Fig. 2: MitoTam improves metabolic profile and attenuates senescence markers in mice fed high-fat diet.
C57BL/6 mice fed with SD (standard diet), HFD (high-fat diet) or HFD + PF (pair feed high-fat diet) were treated with MitoTam (MT; 2 mg/kg body weight dissolved in 4% ethanol in corn oil) or the vehicle (CO) given i.p. twice per week for a period of 4 weeks. a, e Total body weight was taken once per week throughout the experiment; (a; n = 10; HFD + CO vs. HFD + MT: 3rd week p = 0.002; 4th week p < 0.001), (e; HFD + CO n = 6, HFD + MT, HFD + PF n = 7 animals), Δ body weight was calculated as the difference between initial and final body weight; (a; HFD + CO vs. HFD + MT p < 0.001); (e; HFD + CO vs. HFD + MT p < 0.001, HFD + CO vs. HFD + PF p = 0.032, HFD + MT vs. HFD + PF p = 0.019). b, f Visceral adipose tissue (VAT) weight at the end of the experiment; (b; n = 10; SD + CO vs. HFD + CO p < 0.001, HFD + CO vs. HFD + MT p < 0.001), (f, HFD + CO n = 6; HFD + MT, HFD + PF n = 7; HFD + CO vs. HFD + MT p = 0.040). c, d FI was expressed in kcal/day per mouse; c (n = 10; 1st week HFD + CO vs. HFD + MT p = 0.012; 3rd week HFD + CO vs. HFD + MT p = 0.0103; 4th week HFD + CO vs. HFD + MT p = 0.0146), (d, HFD + CO n = 6, HFD + MT, HFD + PF n = 7; 2nd week HFD + CO vs. HFD + MT and HFD + PF p = 0.0162; 3rd week HFD + CO vs. HFD + MT and HFD + PF p = 0.0296; 4th week HFD + CO vs. HFD + PF p = 0.0181). g Histological samples of VAT were stained with H&E. h The level of mRNA of p16Ink4a in epididymal adipose tissue (EAT) was assessed by qRT-PCR (SD + CO n = 8; SD + MT, HFD + CO n = 10, HFD + MT n = 9; SD + CO vs. HFD + CO p < 0.001, HFD + CO vs. HFD + MT p = 0.015); % of SA-β-gal-positive tissue in EAT is shown as bar graph (left) and representative tissue is presented (right; blue color) (n = 6; SD + CO vs. HFD + CO p = 0.024, HFD + CO vs. HFD + MT p = 0.001). i % of SA-β-gal-positive tissue in EAT is shown as bar graph (left) and representative tissue is presented (right; blue color) (HFD + CO n = 6; HFD + MT, HFD + PF n = 7; HFD + CO and HFD + PF vs. HFD + MT p < 0.001). j, k Fasting blood glucose was determined at the beginning and at the end of the experiment, both after 16 h of fasting, and area under the oGTT curve (AUC) was estimated (j, n = 10; glucose before treatment SD vs. HFD p < 0.001, after treatment SD + CO vs. HFD + CO p < 0.001, HFD + CO vs. HFD + MT p < 0.001; AUC SD + CO vs. HFD + CO p < 0.001, HFD + CO vs. HFD + MT p < 0.001); (k, HFD + CO n = 6, HFD + MT, HFD + PF n = 7; glucose after treatment HFD + PF vs. HFD + MT p = 0.032; AUC HFD + CO vs. HFD + MT p < 0.001, HFD + PF vs. HFD + MT p = 0.018). For a, e (∆ B.W.), b, f, h–k One-way ANOVA, Tukey’s comparison multiple test was used. For a, e (total B.W.), c, d 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.
