Extended Data Fig. 6: Halting APP overexpression reverses the obese phenotypes (related to Fig. 6).

a–d, APP-overexpressing mice (APP+) were fed with HFD/Dox diets for 8 weeks and were divided into two groups, one group continuously on HFD/Dox feeding (Keep Dox) and the other group fed with HFD without Dox (Withdraw Dox). Two groups of mice are subject to the following metabolic analyses (n = 6 mice per group). a, Body weight for 12 weeks. b, Ex vivo mitochondrial respiration (OCR) in sWAT fat pads from both groups, n = 10 tissues per group. c,d, Glucose levels at different time points from OGTT (c) and ITT experiments (d). e,f,h, Control mice (APP–) were fed with HFD/Dox diets for 8 weeks, and the cohorts were divided into two groups, one group continuously on HFD/Dox feeding and the other group fed with HFD without Dox. Two groups of mice were subjected to the following metabolic analyses. e, Body weights for the 12-week exposure (n = 6 mice per group). f, Ex vivo mitochondrial respiration (OCR) in sWAT fat pads from both groups (n = 10 tissues per group). h, Glucose levels at different time points from (n = 6 mice per group) OGTT experiments. g, Combined high-resolution respirometry measured in isolated mitochondria from four groups including control or APP transgenic mice kept with or without Dox feeding, n = 5 mice per group. i,j, AT inflammatory and liver steatosis phenotypes in control or APP transgenic mice kept with or without Dox feeding. i, Representative H&E staining images for sWAT. j, Representative H&E staining images of liver tissues from four groups. Images are chosen from three independent experiments. For all the statistics: data are presented as mean ± s.e.m. of biologically independent samples. Two-way ANOVA followed by a Tukey post-test (a–h), and no statistical significance was found in e, f and h.