Extended Data Fig. 4: Response of high-fat diet-fed Gdf15−/− and Gfral−/− mice to metformin.
From: GDF15 mediates the effects of metformin on body weight and energy balance
a, Circulating GDF15 levels in high-fat diet-fed Gdf15+/+ and Gdf15−/− mice given oral dose of metformin (300 mg kg−1) once daily for 11 days. Data are mean ± s.e.m., mice as in Fig. 2a. All Gdf15−/− samples were below lower limit of the assay (<2 pg ml−1); P values by two-way ANOVA with Tukey’s correction for multiple comparisons. b, Circulating GDF15 levels in high-fat diet-fed Gfral+/+ and Gfral−/− mice given oral dose of metformin (300 mg kg−1) once daily for 11 days. Data are mean ± s.e.m., mice as in Fig. 2c; P values by two-way ANOVA with Tukey’s correction for multiple comparisons. c, Cumulative food intake in high-fat diet fed Gfral+/+ and Gfral−/− mice on a high-fat diet given an oral dose of metformin (300 mg kg−1) once daily for 11 days. Data are mean ± s.e.m., mice as in Fig. 2c; no statistically significant difference in vehicle versus metformin by two-way ANOVA. d, Fat mass (left) and lean mass (right) in metformin-treated obese mice dosed with anti-GFRAL antagonist antibody weekly for five weeks, starting four weeks after initial metformin exposure (mice as in Fig. 2d). Body composition was measured using MRI after 4 weeks of metformin exposure, before receiving anti-GFRAL (week 4), after 6 weeks of metformin exposure and 2 weeks after receiving anti-GFRAL (week 6) and after 9 weeks of metformin exposure and 5 weeks after receiving anti-GFRAL (week 9). Data are mean ± s.e.m. (n = 7, vehicle + control IgG and metformin + anti-GFRAL; n = 8, other groups); P values by two-way ANOVA with Tukey’s correction for multiple comparisons.
