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. 2012 Feb 1;26(3):259–270. doi: 10.1101/gad.180406.111

Figure 1.

Figure 1.

Temporal Hif1α inactivation attenuates adipose tissue expansion and protects from obesity-associated pathologies. (A) Schematic representation of the NCD/NCD (top panel) and HFD/HFD (bottom panel) protocols. All Hif1α iC and Hif1α icKO mice were initially maintained on a NCD to 4 wk of age, after which, Hif1α iC and Hif1α icKO littermates were randomly assigned to either the NCD/NCD or HFD/HFD protocol. NCD/NCD and HFD/HFD mice were maintained on a NCD or HFD for 14 wk thereafter, and tamoxifen was administered to both Hif1α iC and Hif1α icKO mice. The mice were maintained on either the NCD or HFD feeding protocol, respectively, following tamoxifen administration. GTT and ITT measurements were taken prior to Hif1α inactivation at weeks 16 and 17, respectively, and at weeks 14 and 15 post-Hif1α inactivation, respectively. (B) Visceral WAT and intrascapular BAT biopsies of tamoxifen-induced NCD/NCD- and HFD/HFD-maintained Hif1α iC(T) and Hif1α icKO(T) mice were assessed for Hif1α mRNA expression by qPCR. All values were normalized internally to 18S RNA expression and to the Hif1α iC(T) control, respectively. (*) P < 0.01 versus control, set at 1.0. Data are mean ± SEM of values from five mice per group. (C) Visceral WAT and BAT sections of Hif1α iC(T) and Hif1α icKO(T) mice maintained on the HFD/HFD protocol for 16 wk post-tamoxifen induction were stained with phalloidin to mark actin and the cell periphery and counterstained with DAPI. Confocal microscopic imaging was performed, and the cell surface area was quantified. Surface area measurements relative to Hif1α iC(T) sections are shown, which was set at 1.0. (*) P < 0.01. Data are mean ± SEM of values from five mice per group. (D) Hif1α iC(T) (n = 8 NCD/NCD; n = 10 HFD/HFD) and Hif1α icKO(T) (n = 7 NCD/NCD; n = 12 HFD/HFD) mice were assessed for changes in body weight at the indicated time points. (*) P < 0.05 versus Hif1α iC(T) HFD/HFD; (%) P < 0.05 versus Hif1α iC(T) NCD/NCD and Hif1α icKO(T) NCD/NCD. Data are mean ± SEM of values from each group. (E,F) Individual organs of Hif1α iC(T) (n = 8 NCD/NCD; n = 10 HFD/HFD) and Hif1α icKO(T) (n = 7 NCD/NCD; n = 12 HFD/HFD) mice were excised and weighed 16 wk post-tamoxifen induction. eWAT, rpWAT, and SKM indicate epididymal WAT, retroperitoneal WAT, and skeletal muscle, respectively. (*) P < 0.05 versus Hif1α iC(T). Data are mean ± SEM of values from each group. (G) GTT measurements of Hif1α iC(T) (n= 8 NCD/NCD; n = 10 HFD/HFD) and Hif1α icKO(T) (n = 7 NCD/NCD; n = 12 HFD/HFD) mice prior to tamoxifen-mediated Hif1α excision at week 16. (*,%) P < 0.05 versus Hif1α iC(T) NCD/NCD. Data are mean ± SEM of values from each group. (H) ITT measurements of Hif1α iC(T) (n = 8 NCD/NCD; n = 10 HFD/HFD) and Hif1α icKO(T) (n = 7 NCD/NCD; n = 12 HFD/HFD) mice prior to tamoxifen-mediated Hif1α excision at week 17. (*,%) P < 0.05 versus Hif1α iC(T) NCD/NCD. Data are mean ± SEM of values from each group. (I) GTT measurements of Hif1α iC(T) (n = 8 NCD/NCD; n = 10 HFD/HFD) and Hif1α icKO(T) (n = 7 NCD/NCD; n = 12 HFD/HFD) mice at 16 wk post-tamoxifen-mediated Hif1α excision. (*,%) P < 0.05 versus Hif1α iC(T) NCD/NCD. Data are mean ± SEM of values from each group. (J) ITT measurements of Hif1α iC(T) (n = 8 NCD/NCD; n = 10 HFD/HFD) and Hif1α icKO(T) (n = 7 NCD/NCD; n = 12 HFD/HFD) mice at 17 wk post-tamoxifen-mediated Hif1α excision. (*) P < 0.05 versus Hif1α iC(T) NCD/NCD. Data are mean ± SEM of values from each group. (K) Intrascapular BAT and visceral WAT biopsies of Hif1α C and Hif1α BATcKO mice maintained on either NCD or HFD were assessed for Hif1α mRNA expression by qPCR. All values were normalized internally to 18S RNA expression and to the Hif1α C control. (*) P < 0.01 versus control, set at 1.0. Data are mean ± SEM of values from seven mice per group. (L) Hif1α f/f (n = 10 NCD; n = 12 HFD) and Hif1α BATcKO (n = 8 NCD; n = 12 HFD) mice were maintained on either a NCD or HFD. Body weight measurements were taken at the indicated time points throughout the course of the protocol. (*,%) P < 0.05 versus NCD group. Data are mean ± SEM of values from each group.