Comparison of western diet-induced obesity and streptozotocin mouse models: insights into energy balance, somatosensory dysfunction, and cardiac autonomic neuropathy

Figures

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  FIGURE 1. Low doses of STZ in WD-fed mice reduces serum insulin secretion and impairs peripheral insulin signaling. (A) Experimental paradigm where 6-week-old mice were given normal chow (NC) or western diet (WD) for 26 weeks. At week 7, mice were injected with multiple doses of streptozotocin (STZ) or vehicle. (B) Week 26 glucose tolerance test (GTT) and (C) area under the curve (AUC). (D) Blood glucose measurements after 4 h fast. (E) Week 26 fasting serum insulin levels, (F) serum insulin levels 30 min post-glucose injection during GTT, and (G) calculated Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores (n = 3/group). (H) The ratio of pAKT to AKT protein levels from soleus muscle with (I) representative immunoblot images, where mice were given intraperitoneal injections of either insulin (.75 U/kg bodyweight) or vehicle before euthanization at week 26 (n = 3–4/group) (two-way ANOVA). Statistical analyses were done using one-way ANOVA unless reported otherwise. Data are mean ± SEM (*p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.0001).

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  FIGURE 2. WD and WD + STZ mice display features of early cardiac dysfunction concomitant with a decrease in autonomic innervation. Week 26 echocardiography measurements of (A) heart rate, (B) ejection fraction, and (C) global longitudinal strain (GLS). (D) Heart rate variability assessment of mean RR interval, (E) standard deviation of NN intervals (SDNN), and (F) root mean square of successive differences between normal heartbeats (RMSSD). (G) Representative images of tyrosine hydroxylase (TH)+ cardiac fibers (TH-red, nucleus-DAPI/blue) and (H) calculated TH+ fiber projection length. (I) Relative TH protein levels compared to total protein staining with (J) representative immunoblot images. (K) Relative Choline Acetyltransferase (ChAT) levels compared to total protein staining with (L) representative immunoblot images. Statistical analyses were done using one-way ANOVA (n = 6–7/group). Data are mean ± SEM (*p < 0.05, **p < 0.01, ****p < 0.0001).

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  FIGURE 3. WD and WD + STZ mice have similar body composition and energy expenditure profiles. (A) Weekly weight measurements where week 0 is the start of diet feeding (Dotted line indicates injection at week 7, Repeated measures two-way ANOVA, *p < 0.05 WD/WD + STZ vs. NC). (B) Body composition analysis of fat mass and (C) lean mass at week 21 of the paradigm. (D) Hourly and (E) cumulative energy expenditure profiles over 72 h. (F) Change in energy expenditure during 4-h cold exposure at 4°C, and (G) area under the curve (AUC). Statistical analyses were done using one-way ANOVA unless reported otherwise (n = 6–7/group). Data are mean ± SEM (*p < 0.05, **p < 0.01, ****p < 0.0001).

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  FIGURE 4. WD and WD + STZ mice have similar respiratory exchange ratios but different feeding behaviors. (A) Hourly and (B) cumulative respiratory exchange ratio (RER) measured during indirect calorimetry. (C) Cumulative food intake and (D) water intake during indirect calorimetry. Statistical analyses were done using one-way ANOVA (n = 6–7/group). Data are mean ± SEM (*p < 0.05, ***p < 0.005, ****p < 0.0001).