Fig. 2.

Diet-induced obese mice chronically lose fat tissue mass by induction of adipose tissue-specific IR knockout while, in parallel, mice are protected from diet-induced obesity when knockout is carried out before the initiation of HFD feeding. (a) Body mass and (b) fat mass of HFD-induced obese mice before and after induction of IR knockout by tamoxifen in adipose tissue (n = 5–16 for IR^fl/fl; n = 5–16 for iFIRKO). (c) Ad libitum-fed blood glucose after two consecutive periods of induction of IR knockout in HFD-induced obese mice (n = 4–7 for IR^fl/fl; n = 5–9 for iFIRKO). (d) Effect of HFD on body mass of lean mice after induction of adipose tissue-specific IR deletion (n = 11 for IR^fl/fl; n = 5 for iFIRKO). (e) Evaluation of body composition and EchoMRI measurements of lean and fat mass in iFIRKO and IR^fl/fl littermate controls before and after an 11 week HFD challenge. Adipose tissue-specific IR knockout was induced at the initiation of the HFD challenge (n = 11 for IR^fl/fl; n = 5 for iFIRKO; d, days). (f–h) Total adipocyte number in whole iBAT, ingWAT and epiWAT depots 1 week after tamoxifen induction, as measured by quantitative PCR for the evaluation of all cells that demonstrated the loxPStoploxP-tdRFP recombination (n = 12 for IR^fl/fl; n = 14 for iFIRKO). Grey bars in (a–d) indicate time period of tamoxifen gavage. Data are mean ± SEM. Student’s t test: **p < 0.01, ***p < 0.001 for iFIRKO vs IR^fl/fl or as shown. In (a, b, d) difference is significant for all time points below the line. d, days; Tam, tamoxifen