Journal: Science Advances

Article Title: The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21

doi: 10.1126/sciadv.adt3142

Figure Lengend Snippet: ( A ) Principal components analysis from RNA-seq of vehicle- or HF (100 μg/kg)–treated mouse liver and WAT tissues (WAT, n = 3; liver, n = 5). ( B ) Volcano plot of significantly down-regulated (blue) and up-regulated (red) genes in WAT from mice as described in (A) (|Log 2 FC| > 1.5, P value <0.01). ( C ) Volcano plot of significantly down-regulated (blue) and up-regulated (red) genes in liver from mice as described in (A) (|Log 2 FC| > 1.5, P value<0.01). ( D ) The nine-quadrant plot shows the correlation between differentially expressed proteins in the WAT and liver groups. ( E ) Heatmap analysis of differentially expressed genes in livers and WAT from vehicle- and HF-treated mice. ( F ) Reactome enrichment pathway analysis implicates GCN2/ATF4-associated cellular responses to stress pathway in HF-treated group. Significantly overrepresented pathways (FDR < 0.05) were grouped and depicted. The size of the circles corresponds to the number of genes in each module. ( G ) Levels of ATF4 protein in liver tissues of DIO mice injected with vehicle or HF (100 μg/kg), n = 5. ( H ) Serum GDF15 (vehicle group, n = 7; HF group, n = 6), FGF21 (vehicle group, n = 7; HF group, n = 6), leptin ( n = 7), and adiponectin ( n = 7) protein levels of DIO mice injected with HF (100 μg/kg) for 8 week. Data are means ± SEM. P values for the data of GDF15 and leptin were calculated by two-sided unpaired t tests. P values for the data of FGF21 and adiponectin were calculated by two-sided unpaired t tests with Welch’s correction.

Article Snippet: Levels of mouse serum GDF15 were measured by the Mouse/Rat GDF-15 Quantikine ELISA Kit (R&D Systems, MGD150, MN, USA).

Techniques: RNA Sequencing, Injection

Journal: Science Advances

Article Title: The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21

doi: 10.1126/sciadv.adt3142

Figure Lengend Snippet: ( A ) Serum GDF15 protein levels of DIO mice injected with HF (100 μg/kg) at indicated time [ n = 5, except for the vehicle group at 6 hours ( n = 4)]. ( B ) Serum FGF21 protein levels of DIO mice injected with HF (100 μg/kg) at indicated time [ n = 5, except for the vehicle group at 6 hours ( n = 4)]. ( C ) Levels of Gdf15 and Fgf21 mRNAs in indicated organs of DIO mice injected with vehicle or HF (100 μg/kg) at 1 hour ( n = 5). ( D and E ) Protein levels (p-GCN2, GCN2, ATF4, p-eIF2α, eIF2α, GDF15, and FGF21) in mouse primary hepatocytes (MPH). ( F ) Levels of Atf4 , Gdf15 , and Fgf21 mRNAs in MPH treated with HF (25 nM) in the presence or absence of proline (4 mM) for 24 hours ( n = 5). ( G ) Levels of Atf4 , Gdf15 , and Fgf21 mRNAs in control siRNA (si NC ) or Atf4 siRNA (si Atf4 )–treated MPH exposed to HF (25 nM) ( n = 5). ( H ) Protein levels (GDF15, and FGF21) in MPH. Data are presented as means ± SEM. Data in (A), 3 and 12 hours in (B) were calculated using two-sided unpaired t tests with Welch’s correction. Data in 6 hours in (B) were analyzed by nonparametric tests. Bar graphs in (C) analyzed by two-way ANOVA followed by Bonferroni’s multiple comparisons test. Data in (F) and (G) analyzed by two-way ANOVA followed by Tukey’s multiple comparisons test.

Article Snippet: Levels of mouse serum GDF15 were measured by the Mouse/Rat GDF-15 Quantikine ELISA Kit (R&D Systems, MGD150, MN, USA).

Techniques: Injection, Control

Journal: Science Advances

Article Title: The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21

doi: 10.1126/sciadv.adt3142

Figure Lengend Snippet: ( A to F ) Eight-week-old male WT and Gdf15 KO mice were fed with HFD for 8 weeks. WT and Gdf15 KO mice were then randomly assigned to vehicle or HF (100 μg/kg) group and injected every 2 days for 8 weeks. (B) Serum GDF15 levels. (C) Body weight and % body weight change (WT-Veh, n = 5; WT-HF, n = 6; Gdf15 KO-Veh, n = 7; Gdf15 KO-HF, n = 7). (D) Fat mass and lean mass (% body weight). (E) Weights of adipose tissues. (F) Serum TC and TG levels (WT-Veh, n = 5; WT-HF, n = 6; Gdf15 KO-Veh, n = 6; Gdf15 KO-HF, n = 7). ( G ) Cumulative food intake of single cage WT or Gdf15 KO mice treated with vehicle or HF (100 μg/kg) ( n = 4). ( H ) EE in Gdf15 KO mice treated with vehicle or HF (100 μg/kg) (vehicle group, n = 9; HF group, n = 10). ( I ) UCP1 protein abundance in iBAT of HF (100 μg/kg)–treated WT and Gdf15 KO mice ( n = 3). Data are presented as means ± SEM. Data in (B) to (F) were determined through two-way ANOVA followed by Bonferroni’s multiple comparisons test. Data in (G) were determined through two-way ANOVA. Data in (H) were determined through ANCOVA using body mass as a covariate.

Article Snippet: Levels of mouse serum GDF15 were measured by the Mouse/Rat GDF-15 Quantikine ELISA Kit (R&D Systems, MGD150, MN, USA).

Techniques: Injection, Quantitative Proteomics