Fig. 1: TRF reduces obesity and improves metabolic dysregulation in obese HFD-fed postmenopausal mouse models. | Nature Communications

Fig. 1: TRF reduces obesity and improves metabolic dysregulation in obese HFD-fed postmenopausal mouse models.

From: Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models

Fig. 1

a Schematic of female postmenopausal mouse models showing bilateral ovariectomy (OVX) or daily 4-vinylcyclohexene diepoxide (VCD) treatment over 15 days in C57BL/6 mice. b Levels of luteinizing hormone (LH), testosterone, progesterone, and dihydroandrosterone (DHEA) in plasma from OVX and VCD mice compared with control (Ctl) ovary intact mice (number of mice n = 3 for Ctl, n = 8 for OVX, n = 4–6 for VCD; **p < 0.0, ****p < 0.0001 by one-way ANOVA with Tukey’s multiple comparisons test). Ctl mice are colored blue, OVX mice orange, and VCD mice green. c, e Weekly body weights of OVX and VCD mice on ad libitum normal chow (NC), ad libitum high-fat diet (AL), and time-restricted high-fat diet (TRF) after initiation of the TRF protocol (n = 8 for NC, n = 10 for AL, n = 10 for TRF in c; n = 7 for NC, n = 7 for AL, n = 8 for TRF in e; *p < 0.05, **p < 0.01, ****p < 0.0001 by two-way ANOVA with Tukey’s multiple comparisons test). The vertical bar indicates differences between NC and the AL and TRF groups. The horizontal bar indicates differences between AL and TRF at those time points. NC mice are colored blue, AL mice orange, and TRF mice green in all figure panels. d, f Daily mean food intake in OVX and VCD mice (n = 8 for NC, n = 10 for AL, n = 10 for TRF in d, n = 8 for NC, n = 8 for AL, n = 8 for TRF in f; **p < 0.01, ****p < 0.0001 by one-way ANOVA with Tukey’s multiple comparisons test). g, i Intraperitoneal-glucose tolerance test (GTT) on female OVX or VCD mice after 7 weeks of TRF (n = 7 for NC, n = 10 for AL, n = 9 for TRF in g; n = 7 for NC, n = 7 for AL, n = 8 for TRF in i; *p < 0.05, **p < 0.01, ****p < 0.0001 by two-way ANOVA with Tukey’s multiple comparisons test). The horizontal bar indicates differences between AL and TRF at those time points. h, j Fasting blood glucose (FBG) levels at the end of the study in OVX and VCD mice (h, n = 8 for NC, n = 10 for AL, n = 10 for TRF, in j; n = 7 for NC, n = 7 for AL, n = 8 for TRF; *p < 0.05, **p < 0.01, ****p < 0.0001 by one-way ANOVA with Tukey’s multiple comparisons test). k, m Intraperitoneal-insulin tolerance test (ITT) in OVX or VCD mice after 8 weeks of TRF (n = 8 for NC, n = 10 for AL, n = 10 for TRF in k; n = 7 for NC, n = 7 for AL, n = 8 for TRF in m; *p < 0.05, **p < 0.01, ****p < 0.0001 by two-way ANOVA with Bonferroni’s multiple comparisons test). l, n Fasting insulin levels at the end of the study in OVX and VCD mice (n = 6 for NC, n = 7 for AL, n = 8 for TRF in l; n = 7 for NC, n = 7 for AL, n = 8 for TRF in n; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by one-way ANOVA with Tukey’s multiple comparisons test). For b–n, asterisks show statistical significance TRF vs AL or as shown. o–q Fasting glucose, ketone, and glucose–ketone index over 24 h in OVX mice n = 8 for AL, n = 9 for TRF. Period of fasting indicated by yellow bar, and period of feeding indicated by purple bar. Asterisks indicate statistical significance between AL and TRF (*p < 0.05, **p < 0.01, ****p < 0.0001), whereas dots indicate statistical significance for TRF vs 6 am (ZT0), (●p < 0.05, ●●p < 0.01, ●●●p < 0.001, ●●●●p < 0.0001) by two-way ANOVA with Bonferroni’s multiple comparisons test. For b–q, all data are presented as mean ± SEM with n representing the number of mice per group.

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