The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet

Abstract

Obesity and prediabetes are the two strongest risk factors of type 2 diabetes. It has been reported that TOTUM-63, a polyphenol-rich plant extract, has beneficial effects on body weight (BW) and insulin resistance in mice fed a high fat diet (HFD). The study aim was to determine whether high-intensity interval training (HIIT) and/or TOTUM-63 supplementation improved body composition and glycemic control and gut microbiota composition in a Western diet-induced obesity rat model. Wistar rats received a standard diet (CTRL; control; n = 12) or HFD (HFD; n = 48) for 16 weeks. Then, HFD rats were divided in four groups: HFD, HFD + TOTUM-63 (T63), HFD + HIIT (HIIT), and HFD + HIIT +T63 (HIIT + T63). Training was performed 4 days/week for 12 weeks. TOTUM-63 was included in diet composition (2%). The HIIT + T63 combination significantly limited BW gain, without any energy intake modulation, and improved glycemic control. BW variation was correlated with increased α-diversity of the colon mucosa microbiota in the HIIT + T63 group. Moreover, the relative abundance of Anaeroplasma, Christensenellaceae and Oscillospira was higher in the HIIT + T63 group. Altogether, these results suggest that the HIIT and TOTUM-63 combination could be proposed for the management of obesity and prediabetes.

Keywords: body composition; glycemic control; high-intensity interval training; microbiota; plant extract supplementation.

Figure 1

Study design. Rats were randomized in two groups: control (CTRL; n = 12) and High-Fat Diet (HFD; n = 48) for 16 weeks (obesity induction). Then, the HFD group was divided in four groups (n = 12/group) matched for weight, fat mass and fasting blood glucose: HFD, TOTUM-63 (T63), High-Intensity Interval Training (HIIT), and HIIT + T63 (intervention period for 12 weeks). In the HIIT and HIIT + T63 groups, “no runner” rats were excluded from the study. Two rats from the T63 group died during glucose gavage due to intubation mishandling. Finally, 41 rats were included in the analysis (HFD: n = 12; T63: n = 10; HIIT: n = 10 and HIIT + T63: n = 9).

Figure 2

Effect of obesity induction on body weight (BW) (A), total fat mass (FM) (B), total lean body mass (LBM) (C), fasting glycemia (D), fasting insulinemia (E), blood glucose during the oral glucose tolerance test (OGTT) (F) and total area under the curve of glucose (AUC_glucose) (G). * p < 0.05, ** p < 0.005, *** p < 0.0005, G: group effect, T: time effect, G × T: group × time effect. CTRL: control group, HFD: high-fat diet.

Figure 3

Mean energy intake in the four groups (A). Changes in body weight (ΔBW) (B,C), fat mass (ΔFM) (D), lean body mass (LBM) (E), and epididymal adipose tissue (AT) (F) at the end of the 12-week intervention. * p < 0.05, ^µµ p < 0.005: HFD vs. T63, ^$ p < 0.05, ^$$ p < 0.005: HIIT vs. T63, ^§ p < 0.05, ^§§ p < 0.005, ^§§§ p < 0.0005: HIIT vs. HFD, ^£ p < 0.05, ^££ p < 0.005: HIIT + T63 vs. T63, ^# p < 0.05, ^## p < 0.005: HIIT + T63 vs. HFD. ΔBW = ((Week 28 BW − Week 16 BW)/Week 16 BW) × 100; ΔFM = ((Week 28 FM − Week 16 FM)/Week 16 FM) × 100, G: group effect, T: time effect, G × T: group × time effect.

Figure 3

Mean energy intake in the four groups (A). Changes in body weight (ΔBW) (B,C), fat mass (ΔFM) (D), lean body mass (LBM) (E), and epididymal adipose tissue (AT) (F) at the end of the 12-week intervention. * p < 0.05, ^µµ p < 0.005: HFD vs. T63, ^$ p < 0.05, ^$$ p < 0.005: HIIT vs. T63, ^§ p < 0.05, ^§§ p < 0.005, ^§§§ p < 0.0005: HIIT vs. HFD, ^£ p < 0.05, ^££ p < 0.005: HIIT + T63 vs. T63, ^# p < 0.05, ^## p < 0.005: HIIT + T63 vs. HFD. ΔBW = ((Week 28 BW − Week 16 BW)/Week 16 BW) × 100; ΔFM = ((Week 28 FM − Week 16 FM)/Week 16 FM) × 100, G: group effect, T: time effect, G × T: group × time effect.

Figure 4

Effects of T63 supplementation and/or HIIT on (i) Fasting glycemia (A), Fasting insulinemia (B), and HOMA-IR (C) and on (ii) blood glucose (D,E), and insulin (F,G) levels during the oral glucose tolerance test (OGTT). * p < 0.05. AUC: area under the curve, G: group effect, T: time effect, G × T: group × time effect.

Figure 4

Effects of T63 supplementation and/or HIIT on (i) Fasting glycemia (A), Fasting insulinemia (B), and HOMA-IR (C) and on (ii) blood glucose (D,E), and insulin (F,G) levels during the oral glucose tolerance test (OGTT). * p < 0.05. AUC: area under the curve, G: group effect, T: time effect, G × T: group × time effect.

Figure 5

Effects of T63 supplementation and/or HIIT on GLUT4 protein content (A), citrate synthase (CS) activity (B), and OXPHOS complex protein content (C) in soleus. * p < 0.05, ** p < 0.005, *** p < 0.0005, G: group effect, T: time effect, G × T: group × time effect.

Figure 6

Effects of T63 supplementation and/or HIIT on oxidized low-density lipoproteins (oxLDL) (A), advanced oxidation protein products (AOPP) (B), superoxide dismutase (SOD) activity (C), and glutathione peroxidase (GP_X) activity (D) in plasma. * p < 0.05, ** p < 0.005, G: group effect.

Figure 7

Mucosa-associated microbiota composition analyzed by 16S rRNA gene sequencing in colon DNA samples (Illumina MiSeq system). Shannon index (A), correlation between Shannon index and body weight change (%) (ΔBW) (B). Unweighted Unifrac analysis clustered in four groups (C) and two groups (T63 and no T63) (D), G: group effect. * p < 0.05, ** p < 0.005.

Figure 8

Taxonomy at the phylum (A) and family (B) levels for the four groups. Relative abundance (%) of specific bacterial types in the mucosa-associated microbiota at the end of the 12-week intervention (C–E) * p < 0.05, ** p < 0.005, *** p < 0.0005, G: group effect.

Figure 9

Heat map showing the association of the abundance of the indicated microbiota components with body composition (A), and glucose homeostasis parameters (B). * p < 0.05, ** p < 0.005, *** p < 0.005. BW: body weight; FM: fat mass; Δ: delta; AUC: area under the curve; CS: citrate synthase.