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. 2023 Jun 28;619(7968):143–150. doi: 10.1038/s41586-023-06249-4

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 6 — A, Body weight in Comprehensive Lab Animal Monitor System (CLAMS). Data are means ± SEM, n = 10 mice (WT-vehicle, WT-GDF15 and WT-pair-fed), n = 7 mice (KO-Pair-fed) and n = 6 mice (KO-GDF15). P values by one-way ANOVA with Dunnett’s multiple comparisons test. B, Animal activity during 12h-light/dark circle. Data are means ± SEM, n = 10 mice (WT-vehicle, WT-GDF15 and WT-pair-fed), n = 7 mice (KO-Pair-fed) and n = 6 mice (KO-GDF15). C, Average respiratory exchange ratios (RER) curves in WT and GFRAL KO mice and quantification of average 24h RER. Data are means ± SEM, n = 10 mice/group. P values by one-way ANOVA with Šídák’s multiple comparisons test. D, Average lipid oxidation curves in WT and GFRAL KO mice and quantification of average 24h lipid oxidation. Data are means ± SEM, n = 10 mice/group. P values by one-way ANOVA with Šídák’s multiple comparisons test. E, Average carbohydrate oxidation (CHO) curves in WT and GFRAL KO mice and quantification of average 24h CHO. Data are means ± SEM, n = 10 mice/group. P values by one-way ANOVA with Šídák’s multiple comparisons test. F, Animal activity during 12h-light/dark circle. Data are means ± SEM, n = 6 mice/group. G, Body mass of mice in CLAMS. n = 6 mice/group. H, Experimental scheme for the effects of a single injection of GDF15 on respiratory exchange ratios (RER), lipid oxidation and carbohydrate oxidation (CHO) in WT and beta-less mice. I, Body weight in CLAMS. Data are means ± SEM, n = 8 mice/group. J, Respiratory exchange ratio (RER) over time in WT and beta-less mice. Data are means ± SEM, n = 8 mice/group. K, Average fatty acid oxidation over 24hours. Data are means ± SEM, n = 8 mice/group. P values by one-way ANOVA with Tukey’s multiple comparisons test. L, Average carbohydrate oxidation over 24h. Data are means ± SEM, n = 8 mice/group. P values by one-way ANOVA with Tukey’s multiple comparisons test. M, GDF15 did not change serum norepinephrine. Data are means ± SEM, n = 7 mice/group except vehicle group, n = 6 mice. N, GDF15 did not change norepinephrine in the brown adipose tissue (BAT). Data are means ± SEM, n = 6 mice/group. O, GDF15 did not change norepinephrine in the liver. Data are means ± SEM, n = 5 mice/group. P values by one-way ANOVA with Tukey’s multiple comparisons test.

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