Extended Data Fig. 5: (A-G) Triiodothyronine (T3) is unlikely the primary mechanism contributing to increases in the body weight loss and energy expenditure (EE) induced by GDF15.
From: GDF15 promotes weight loss by enhancing energy expenditure in muscle
A, A single dose of GDF15 did not change serum T3. Data are means ± SEM, n = 10 mice/group. B, GDF15 treatment for 6 weeks did not change serum T3. Data are means ± SEM, n = 10 mice/group except GDF15 (5 nmol/kg) and pair-fed groups, n = 9 mice. Statistical analysis was performed by one-way ANOVA with Tukey’s multiple comparisons test. C, Correlation between GDF15 and thyroid-stimulating hormone (TSH) in human plasma (n = 22 participants). The correlation analysis was performed using Pearson’s product-moment correlation (two-sided without adjustment). D, Experimental scheme for examining the effects of the T3 blocker propylthiouracil (PTU) and GDF15 on body mass and EE in mice fed with western diet and housed at thermoneutrality. E, Body weight. Data are means ± SEM, n = 6 mice/group. P values by two-way ANOVA with Tukey’s multiple comparisons test. F, Average 12h-ligh/dark EE. Data are means ± SEM, n = 6 mice/group. P values by one-way ANOVA with Tukey’s multiple comparisons test. G, Animal activity during 12h-light/dark circle. Data are means ± SEM, n = 6 mice/group. (H-M) GDF15 reduces NAFLD and liver inflammation through GFRAL. H, Representative images of paraffin-embedded liver sections stained with H&E. I, Steatosis score, score of ballooning degeneration of hepatocytes, inflammation score, and NAFLD activity score. Data are means ± SEM, n = 10 mice/group. P values by unpaired Mann-Whitney test (two-sided). J, Liver triglycerides (TG). Data are means ± SEM, n = 10 mice/group. P values by one-way ANOVA with Dunnett’s multiple comparisons test. K, Serum alanine aminotransferase (ALT). Data are means ± SEM, n = 10 mice/group. P values by one-way ANOVA with Dunnett’s multiple comparisons test. L, Myeloid cell percentage in the liver. Data are means ± SEM, n = 8 mice (WT-vehicle), n = 6 mice (WT-GDF15), n = 7 mice (WT-pair-fed), n = 4 mice (KO-GDF15 and KO-pair-fed). P values by one-way ANOVA with Tukey’s multiple comparisons test. M, Flowcytometry analysis for immune cell populations, including: CD45+ cell percentage, liver macrophage percentage, and CD4+ T cells percentage in the liver. Data are presented as means ± SEM. Data are means ± SEM, n = 8 mice (WT-vehicle), n = 6 mice (WT-GDF15), n = 7 mice (WT-pair-fed), n = 4 mice (KO-GDF15 and KO-pair-fed).
