Fig. 2

Treatment schedule and validation of the obesity model. a Feeding with regular (control group) or high-fat diet (obese groups) began at month 0, at which time baseline TSPO signals were also assessed in vivo via ¹¹C-PBR-28 PET. ICV cannulas for infusion of vehicle or Aβ were implanted at month 1 and infusion was continuous until month 2. ¹¹C-PBR-28 PET was repeated at months 2 and 3. ¹⁸F-FDG PET was assessed at month 2.5. Behavior testing was carried out at month 3, prior to the final ¹¹C-PBR-28 PET scan. Fasting time points are indicated by arrowheads. Tissues were collected 3 months after the initiation of regular or high-fat diet feeding. b Body weight in mice across the 3-month treatment duration, with significant obesity observed in high-fat fed groups from 1 month. Month 0: F = −11.59, p = 0.38; month 1: F = 11.05, p < 0.001; month 2: F = 10.46, p = 0.001; month 3: F = 9.98, p = 0.003. c Abdominal retroperitoneal fat pad and subcutaneous fat pad weight in mice, confirming increased adiposity in high-fat fed groups. F = 9.21, p = 0.01. d Fasting blood glucose across the 3-month treatment duration, with significant hyperglycemia observed in high-fat fed groups from 1 month. Month 0: F = 0.65, p = 0.59; month 1: F = 19.89, p < 0.001; month 2: F = 5.69, p = 0.006; month 3: F = 4.93, p = 0.01. e Glucose tolerance test in control and obese mice infused with vehicle or Aβ. Obese mice exhibited significant glucose intolerance. Baseline: F = 4.99, p = 0.01; 30-min post-glucose challenge: F = 4.74, p = 0.01; 60-min post-glucose challenge: F = 5.67, p = 0.006. Data presented as mean ± SEM. *p < 0.05 relative to matched time point control mice