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. Author manuscript; available in PMC: 2020 Aug 1.
Published in final edited form as: Nature. 2019 Dec 25;578(7795):444–448. doi: 10.1038/s41586-019-1911-y

Figure 2. GDF15/GFRAL signalling is required for the weight loss effects of metformin on a high fat diet.

Figure 2

a, Percentage change in body weight of Gdf15+/+ and Gdf15-/- mice on a high-fat diet treated with metformin (300mg/kg/day) for 11 days, mean ± SEM, n=6/group except Gdf15+/+ vehicle n=7, P by 2-way ANOVA with Tukey’s correction for multiple comparisons.

b, Cumulative food intake of mice as Figure 2a, P by 2-way ANOVA with Tukey’s correction for multiple comparisons.

c, Percentage change in body weight of Gfral+/+ and Gfral-/- mice on a high-fat diet treated with metformin (300mg/kg/day) for 11 days, mean ± SEM, n=6/groups, P by 2-way ANOVA with Tukey’s correction for multiple comparisons.

d, Percentage change in body weight of metformin-treated obese mice dosed with an anti-GFRAL antagonist antibody, weekly for 5 weeks (yellow), starting 4 weeks after initial metformin exposure (grey),mean ± SEM, n=7 Vehicle + control IgG and Metformin + anti –GFRAL, n=8 other groups, P by 2-way ANOVA with Tukey’s correction for multiple comparisons. “calo” = period in which energy expenditure measured (see Figure 2e), Arrow and “GTT”- timing of oral glucose tolerance test (see Figure 3e-h).

e, ANCOVA analysis of energy expenditure against body weight of mice treated as in Figure 2d, n=6 mice/group. Data are individual mice and P for metformin calculated using ANCOVA with body weight as a covariate and treatment as a fixed factor.