The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity

Figures

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  Figure 1. FFAR3 ablation induces body weight elevation in mice fed with normal chow diet (NCD). (a) Schematic representation of the strategy used to generate Tg2576 mice lacking FFAR3 and the subsequent metabolic assessment. (b) Body weight evaluation of wild type (WT), FFAR3 knockout (FFAR3−/−), Tg2576 (Tg) and Tg2576 FFAR3 knockout mice (Tg-FFAR3−/−). (c) Glucose tolerance test (GTT) and (d) the corresponding AUC quantification. (e) Insulin tolerance test (ITT) and (f) the corresponding AUC quantification. Results are expressed as mean ± SEM and circles in the subfigures represent each individual value (n = 6–9 in each group). ** p < 0.01, *** p < 0.001, two-way ANOVA followed by Tukey.

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  Figure 2. FFAR3 ablation-induced body weight elevation and glucose intolerance is not present in Tg2576 mice fed with high-fat diet (HFD). (a) Schematic representation of the strategy used to generate Tg2576 mice lacking FFAR3, dietary intervention with HFD (starting at 9 months of age), and the subsequent metabolic assessment (at 15 months of age). (b) Body weight evaluation of wild type (WT), FFAR3 knockout (FFAR3−/−), Tg2576 (Tg) and Tg2576 FFAR3 knockout mice (Tg-FFAR3−/−) subjected to HFD. (c) Glucose tolerance test (GTT) and (d) the corresponding AUC quantification of mice subjected to HFD. (e) Insulin tolerance test (ITT) and (f) the corresponding AUC quantification of mice fed on HFD. Results are expressed as mean ± SEM and circles in the subfigures represent each individual value (n = 6–8 in each group). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, two-way ANOVA followed by Tukey.

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  Figure 3. Tg2576 mice exhibit a brain glucose hypermetabolism which is restored upon FFAR3 deletion. (a) PET images of representative mice showing brain 18F-FDG signal in standard uptake value (SUV) and (b) the quantification of positron emission (SUV mean) of wild type (WT), FFAR3 knockout (FFAR3−/−), Tg2576 (Tg) and Tg2576 FFAR3 knockout mice (Tg-FFAR3−/−) fed with NCD. (c) PET images of representative mice showing brain 18F-FDG signal and (d) the quantification of positron emission (SUV mean) of mice subjected to HFD. Results are expressed as mean ± SEM and circles in the subfigures represent each individual value (n = 4–6 in each group). * p < 0.05 and ** p < 0.01, two-way ANOVA followed by Tukey.

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  Figure 4. FFAR3 ablation prevents the cognitive deficiency observed in 15-month-old Tg2576 mice. Spatial memory evaluation by Morris water maze (MWM) (a) memory acquisition and (b) memory retention phase of wild type (WT), FFAR3 knockout (FFAR3−/−), Tg2576 (Tg) and Tg2576 FFAR3 knockout mice (Tg-FFAR3−/−) fed with NCD. MWM (c) memory acquisition and (d) memory retention phase of mice subjected to HFD. Results are expressed as mean ± SEM and circles in the subfigures represent each individual value (n = 6–9 in each group). * p < 0.05 two-way ANOVA followed by Tukey.