Fig. 1.

Liver p53 is engaged in response to a high-fat and high-sugar diet.

(A,B) Male P53rep mice were given an obesogenic HFHS diet at 65-75 days of age or put onto a comparable purified low-fat control diet (chow) and imaged after the indicated days. Representative images (A) and P53rep signal quantification (B) normalised to the initial liver signal identified per mouse. n = 12 chow and n = 13 HFHS mice at 0 days, 50 days, 100 days; n = 7 chow and n = 10 HFHS at 150 days; n = 7 chow and n = 7 HFHS at 200 days, 250 days, 300 days. Data presented as mean +/- range with individual data points and analysed using a two-way ANOVA with Holm-Sidak’s multiple comparisons test and multiplicity-adjusted p values. (C,D) Representative images (C) and quantifications (D) of female mice on same diet and imaging regimen as in (A,B). n = 9 chow and n = 8 HFHS mice for 0 days, 50 days, 100 days; n = 6 chow and n = 6 HFHS for 150 days, n = 6 chow and n = 5 HFHS at 200 days; and n = 6 chow and n = 4 HFHS for 250 days and 300 days. Data presented and analysed as (B). (E,F) Representative images (E) and quantifications (F) of ex vivo P53rep iRFP signal in tissues after 100 days on diet. Organ layout and LUT intensity profile as shown. P53rep intensity normalised to kidney signal in each mouse. n = 1 male and n = 3 female mice in the chow group and n = 3 male and n = 2 female mice in the HFHS group. Data presented as mean +/- SEM and analysed using two-way ANOVA with Holm-Sidak’s multiple comparisons test and multiplicity-adjusted p values. (G) Quantification of IHC staining for CDKN1A/P21 in P53rep mice after 100 days on either HFHS or control (chow) diet. N-numbers and data presentation as in (E,F). Data analysed using an unpaired t-test with Welch’s correction.

n.s., not significant, ∗p <0.05, ∗∗p <0.01, ∗∗∗∗p <0.0001. HFHS, high-fat and high-sugar; IHC, immunohistochemical; P/S, pancreas/spleen.