human gdf15  (Proteintech)

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: Multifaceted validation of GDF15 changes in serum from SICM patients and their clinical associations. (A) GDF15 levels were quantified using the Luminex platform. (B) A volcano plot illustrated the gene expression distribution of GDF15 among differentially expressed genes (DEGs) in whole blood. (C) A heatmap displayed the expression profiles of GDF15 and inflammatory cytokines. (D) Serum GDF15 levels in patients. (E) Pearson correlation analysis demonstrated the association between GDF15 and SOFA score, as well as EF. (F) ROC curves were plotted to assess the diagnostic accuracy of GDF15 and SOFA score in identifying SICM. (G) Multivariate logistic regression analysis was performed to identify independent risk factors for the development of SICM in septic patients. ∗p < 0.05 indicates significant differences; ns: no significant differences.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Biomarker Discovery, Luminex, Gene Expression, Expressing, Diagnostic Assay

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: Upregulation of GDF15 in the SICM model. (A) A schematic workflow for the establishment of the SICM model in C57BL/6J mice via intraperitoneal injection of LPS or saline. (B) Cardiac contractile function parameters, including EF and FS. (C) Serum levels of GDF15 and IL-6. (D) Histopathological analysis of heart tissue, H&E staining (left) and immunohistochemical staining for Ly6G and CD68 (right). Black arrows indicate inflammatory cell infiltration; scale bar: 50 μm. (E) Western blot analysis of GDF15 protein expression in heart tissue. n = 4. (F) qPCR analysis of Gdf15 , Bnp , Il-1β , Il-6 , Icam-1 and Vcam- 1 mRNA levels in heart tissue. (G) Identification of GDF15-positive cells in single-cell RNA-sequencing dataset ( GSE190856 ). (H) qPCR analysis of Gdf15 and Il-1β , Il-6, Nos2, Ptgs2 mRNA expression in BMDM after LPS stimulation. ∗p < 0.05 indicates significant differences; n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Injection, Saline, Staining, Immunohistochemical staining, Western Blot, Expressing, RNA Sequencing

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: GDF15 deficiency exacerbates LPS-induced SICM in mice. (A) Schematic workflow for the establishment of the SICM model in Gdf15 −/− mice. Gdf15 −/− mice were intraperitoneally injected with LPS or saline to induce SICM, with tissue samples collected 24 h post-injection for further analysis. (B) Echocardiographic assessment of EF and FS. (C) H&E staining of heart tissue, black arrows indicate inflammatory cell infiltration. scale bar: 50 μm. (D) CD68 immunofluorescence staining of heart tissue. Blue staining highlights nuclei, red staining identifies CD68 + macrophages; scale bar: 20 μm. (E) qPCR analysis of mRNA expression levels of Bnp , Il-1β, Il-6, and Mcp-1 in heart tissue. n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Injection, Saline, Staining, Immunofluorescence, Expressing

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: MGP exerts anti-inflammatory effects via the MYPT1/AKT/YBX-1 signaling pathway. (A) IP-MS of BMDM to identify the interaction with GDF15. MYPT1 is marked in red. (B) Z-DOCK predicted the interaction domain between GDF15 and MYPT1. Pink represents GDF15, green represents MYPT1, and the boxed region indicates the binding domain. (C) Co-IP combined with Western blot analysis of GDF-15 and MYPT1 binding in macrophages after LPS treatment. (n = 3). (D) Immunofluorescence detection of co-localization between GDF15 (green) and MYPT1 (red), with blue staining for nuclei. Scale bar: 20 μm. (E) Protein expression levels of p -YBX-1, YBX-1, and p -AKT, AKT in BMDM after LPS and/or MGP treatment, with gray-scale intensity analysis of relative expression differences. (F) Representative immunofluorescence images of YBX-1 staining in BMDM after LPS and/or MGP treatment. Blue staining highlights nuclei, and red staining identifies YBX-1. Scale bar: 20 μm ∗p < 0.05, significantly different from control group. #p < 0.05, significantly different from LPS group. n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Protein-Protein interactions, Binding Assay, Co-Immunoprecipitation Assay, Western Blot, Immunofluorescence, Staining, Expressing, Control

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: YBX-1 mediates GDF15-mediated transcriptional regulation of the NLRP3 pathway. (A) qPCR analysis of mRNA expression levels of Nlrp3, Asc , and Il-1β in LPS-stimulated BMDM after Si- Ybx-1 . (B) Western blot analysis of protein expression levels of NLRP3 and IL-1β in LPS-stimulated BMDM after YBX-1 knockdown. (C) qPCR analysis of mRNA expression levels of Nlrp3 and Il-1β in LPS and MGP-treated BMDM after YBX-1 knockdown. (D) Schematic diagram of the luciferase reporter plasmid for the Nlrp3 promoter. (E) Luciferase activity of pcDNA3.1-YBX-1 or empty vector-transfected cells. (F) Luciferase activity after LPS and MGP treatment. n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Expressing, Western Blot, Knockdown, Luciferase, Plasmid Preparation, Activity Assay, Transfection

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: Mechanism of action of macrophage-biomimetic nanocarriers delivering GDF15 to target the YBX-1-NLRP3 axis in SICM. Macrophage-biomimetic nanocarriers loaded with rhGDF15 are targeted to inflammatory sites in the heart, enhancing local drug accumulation, while GDF15 binds to MYPT1 to inhibit YBX-1 phosphorylation and block its nuclear translocation, leading to reduced nuclear YBX-1 expression and decreased transcriptional activity of the Nlrp3 promoter, which suppresses NLRP3 inflammasome assembly and pro-inflammatory cytokine release such as IL-1β, ultimately alleviating macrophage inflammatory responses, myocardial cell injury, and improving cardiac function in SICM.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Phospho-proteomics, Blocking Assay, Translocation Assay, Expressing, Activity Assay

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a ) Pathway analysis from RNA-sequencing of gWAT following 1-hr epinephrine treatment. n = 6 per group. b ) Heat map showing ligand-encoded genes from RNA-sequencing of gWAT following 1-hr epinephrine treatment. n = 6 per group. c ) Circulating GDF15 from age-matched male (saline n = 9 , epinephrine n = 9 ) and female mice (saline n = 10 , epinephrine n = 11 ) following 1-hr epinephrine with fold-change relative to baseline levels (inset). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA with post-hoc test and Tukey’s correction and unpaired two-tail t-test, respectively. d ) Time-course of circulating GDF15 post-saline (RT n = 5 , TN n = 4 ) or epinephrine (RT n = 5 , TN n = 5 ) in mice housed at room temperature (RT ~ 22 °C) or thermoneutrality (TN ~ 29 °C) for 4 weeks. n = 4-5/group. Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA at each time point. e ) Serum epinephrine in control ( n = 9 mice), 1-hr post IP epinephrine ( n = 7 ), and 4-hr physical restraint ( n = 8 ). Data presented as mean ± s.e.m. with p-values calculated using 1-way ANOVA with post-hoc test and Tukey’s correction.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: RNA Sequencing, Saline, Control

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a , Schematic of acute vehicle and adrenaline treatment and analyses. b , Top: time in the centre and total distance travelled during an open-field test 1 h following treatment with adrenaline ( n = 14) or saline ( n = 13). Bottom: representative images of movements of individual mice. Data are presented as mean ± s.e.m. with P values calculated using an unpaired two-tailed t test. c , Principal component analysis of gWAT samples from saline-treated ( n = 6) and adrenaline-treated ( n = 6) mice using VST data from DESeq2. d , Gene-concept network diagram indicating the corresponding enriched Gene Ontology (GO) terms according to DEGs between saline-treated ( n = 6) and adrenaline-treated ( n = 6) gWAT. e , Volcano plot showing DEGs identified between saline- and adrenaline-treated gWAT. The P -adj was calculated using the Benjamini–Hochberg method. FC, fold change. f , Time course of circulating GDF15 before and after adrenaline ( n = 5 mice) or saline ( n = 3) treatment. Data are presented as mean ± s.e.m. with P values calculated using an unpaired two-tailed t test. g , Tissue screen of Gdf15 in mice 1 h after adrenaline ( n = 8) or saline ( n = 9) treatment. Data are expressed relative to the saline-treated liver. Data are presented as mean ± s.e.m. with P values calculated using an unpaired two-tailed t test. ND, not detected; BAT, brown adipose tissue. h , Serum GDF15 levels in mice from the following groups: maintained in their home cage ( n = 5), with cage change for 30 min ( n = 8), group-housed ( n = 6) or single-housed for 3 days ( n = 8). Data are presented as mean ± s.e.m. with P values calculated using an unpaired two-tailed t test. i , Schematic of an acute restraint test in WT and Adrb1 , Adrb2 and Adrb3 triple knockout (BR −/− ) mice. j , Serum GDF15 levels in WT and BR −/− mice following 4 h of tube restraint (WT n = 10, BR −/− n = 14) or the control condition (WT n = 9, BR −/− n = 12). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. k , gWAT Gdf15 expression levels in WT and BR −/− mice following 4 h of tube restraint (WT n = 6, BR −/− n = 7) or the control condition (WT n = 5, BR −/− n = 6). a.u., arbitrary units. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Saline, Two Tailed Test, Triple Knockout, Control, Expressing

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a ) Serum GDF15 levels in children with overweight and obesity with ( n = 23 ) or without ( n = 24 ) diagnosis of anxiety. Data presented as mean ± s.e.m. with p-values calculated using unpaired two-tail t-test. b ) Scatter plot of the SNP-effect on GDF15 and single nucleotide polymorphism (SNP)-effect on nervous anxiety tension or depression in humans by using two sample Mendelian Randomization (2SMR). Data presented as mean ± error bars indicate 95% CI, n = 407,746 participants in UK Biobank. MR analysis was performed by using Simple median method, MR weighted mode estimator, Weighted median method, MR Egger regression, Inverse variance weighted methods. c ) Single SNP analysis of GDF15 on anxiety and depression in humans, Data presented as mean ± error bars indicate 95% CI, n = 407,746 participants in UK Biobank.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Biomarker Discovery

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a ) Serum GDF15 from WT and β-adrenergic receptor knockout (BR -/- ) mice following 2-hr LPS treatment (WT n = 6 , BR -/- n = 6 ) or control (WT n = 6 , BR -/- n = 8 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA. b ) Blood glucose from WT and BR -/- mice following 2-hr LPS treatment (WT n = 6 , BR -/- n = 6 ) or control (WT n = 6 , BR -/- n = 8 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Knock-Out, Control

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a – g , gWAT Atgl expression ( a ), serum nonesterified fatty acids (NEFA) ( b ), gWAT Atf4 expression ( c ), gWAT Chop expression ( d ), gWAT Ppargc1a expression ( e ), gWAT phosphorylated PKA substrates with a representative Western blot image ( f ) and gWAT Gdf15 expression in AdATGL flox/flox (saline n = 5, CL n = 7) and AdATGL −/− (saline n = 7, CL n = 6) mice ( g ). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. h , Circulating GDF15 levels in AdATGL flox/flox (saline n = 5, CL n = 7) and AdATGL −/− (saline n = 7, CL n = 6) mice. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. i , Top: serum GDF15 after 1 h of CL and cilostamide cotreatment in mice ( n = 6 per group). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. Bottom: schematic of the acute restraint test in AdATGL flox/flox and AdATGL −/− mice. j , Serum glycerol levels in AdATGL flox/flox mice (control n = 6, restraint n = 6) and AdATGL −/− mice (control n = 13, restraint n = 11) following restraint. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. k , Left: serum GDF15 in AdATGL flox/flox mice (control n = 6, restraint n = 6) and AdATGL −/− mice (control n = 13, restraint n = 11). Right: graph showing the fold change. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA (left) and an unpaired two-tailed t test (right). l , Glycerol levels in medium from white adipocytes treated with CL and/or ATGListatin ( n = 9 per group; individual data points from three independent experiments). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. m , GDF15 levels in medium from white adipocytes treated with CL and/or ATGListatin ( n = 9 per group; individual data points from three independent experiments). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA. n , Gdf15 expression in adipocytes and SVF from gWAT ( n = 6) and iWAT ( n = 5) of mice. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA. o , Gdf15 expression in adipocytes and SVF from gWAT 1 h after saline ( n = 7) or adrenaline ( n = 9) treatment. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Expressing, Western Blot, Saline, Control, Two Tailed Test

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a ) Fgf21 expression in mouse adipocyte and SVF from gWAT post-saline ( n = 4 per group) or epinephrine ( n = 5 per group). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA with post-hoc test and Tukey’s correction. b ) Leptin expression in mouse adipocyte and SVF from gWAT post-saline ( n = 3 per group) or epinephrine ( n = 4 per group). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA. c ) t-SNE plot of Lin- stromal vascular cells from gWAT of control mice and mice treated with CL for 3 days. Clustering identified 6 major cell types/states. Clusters are highlighted in different colors. The data set was queried for cells expressing Gdf15 . Heatmap shows expression of Gdf15 and other cell-identifying factors in the various identified cell populations. d ) F480/Adgre1 expression in mouse F480+ and F480- fractions of SVF from gWAT 1-hr post-epinephrine treatment (0.5 mg/kg). Data presented as mean ± s.e.m. with n = 3 per group. p-values calculated using 2-way ANOVA. e ) Arg1 and Nos2 expression in bone marrow-derived macrophages (BMDMs) polarized to either M1-like or M2-like. n = 6 per group. Individual data points represent duplicates from 3 independent experiments. Data presented as mean ± s.e.m. with p-values calculated using 1-way ANOVA with post-hoc test and Tukey’s correction. f ) GDF15 levels in media from BMDMs polarized to either M1-like or M2-like for 24-hrs. n = 3 per group. Individual data points represent triplicates from 3 independent experiments. Data presented as mean ± s.e.m. with p-values calculated using 1-way ANOVA with post-hoc test and Tukey’s correction. g ) GDF15 levels in media from M2-like BMDMs treated with epinephrine (1 μM) or tunicamycin (5 ng/mL) for 24-hrs. n = 3 per group. Individual data points represent triplicates from 3 independent experiments. Data presented as mean ± s.e.m. with p-values calculated using 1-way ANOVA with post-hoc test and Tukey’s correction. h ) Volcano plot showing fatty acid transporters identified between M1- and M2-like macrophage populations from scRNA-seq data.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Expressing, Saline, Control, Derivative Assay

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a , Top: t -distributed stochastic neighbour embedding plot of stromal vascular cells from gWAT of mice treated with CL for 3 days. Clustering identified ten major cell types or states. cDCs, conventional dendritic cells; NKT, natural killer T; NK, natural killer; VECs, vascular endothelial cells. Bottom: data were queried for cell clusters expressing Gdf15 . exp., expression. b , Heat map showing the expression of Gdf15 and other cell-identifying factors in the various cell populations identified in scRNA-seq data. c , Data were queried to determine Gdf15 expression in the identified macrophage populations. d , Median normalized average Gdf15 expression in the M2-like, M1-like and macrophage populations from CL-treated mouse scRNA-seq data. The box-and-whisker plot is defined by the median (centre line) with the first quartile (Q1, lower line), third quartile (Q3, upper line), maximum (Q1 − 1.5 × interquartile range) and minimum (Q3 + 1.5 × interquartile range). Whiskers: 1.5 × (Q3 − Q1). P values were calculated using a one-way ANOVA with Benjamini–Hochberg correction for multiple tests. e , Gdf15 expression in mouse F4/80 + and F4/80 − fractions ( n = 3 per group). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. f , Experimental schematic of the isolation, activation and treatment of BMDMs. g , GDF15 levels in medium from BMDMs treated with fatty acids ( n = 3) or tunicamycin ( n = 2). Individual data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. h , Gdf15 expression in BMDMs treated with fatty acids ( n = 3) or tunicamycin ( n = 2). Data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. i , GO enrichment analysis of M1- and M2-like macrophage populations from scRNA-seq data. The P -adj was calculated using the Benjamini–Hochberg method. j , GDF15 levels in medium from M2-like BMDMs treated with rosiglitazone (Rosi) or T0070907 (T007) ( n = 9 per group). Individual data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a one-way ANOVA with post hoc testing and Tukey’s correction. k , GDF15 levels in medium from M2-like BMDMs treated with palmitate (Palm) or T0070907 (T007) ( n = 9 per group). Individual data points represent triplicates from three independent experiments. Data are presented as mean ± s.e.m. with P values calculated using a one-way ANOVA with post hoc testing and Tukey’s correction. f created using BioRender.com .

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Expressing, Whisker Assay, Isolation, Activation Assay

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a , Time in the centre during the open-field test following treatment with saline (WT n = 5 mice, Gfral −/− n = 6) or adrenaline (WT n = 6, Gfral −/− n = 6). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. b , Top: total movement during the open-field test following treatment with saline (WT n = 5, Gfral −/− n = 6) or adrenaline (WT n = 6, Gfral −/− n = 6). Bottom: representative images of movements of individual mice. Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. c , Left: schematic of the acute restraint test. Right: time in the centre during the open-field test following 4 h of tube restraint (WT n = 11 mice, Gfral −/− n = 8) or the control condition (WT n = 10, Gfral −/− n = 9). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. d , Total distance travelled during the open-field test following restraint (WT n = 11 mice, Gfral −/− n = 9) or the control condition (WT n = 10, Gfral −/− n = 9). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA. e , Top: quantification of c-Fos + cells in the bed nucleus of the stria terminalis (BNST), central amygdala (CeA) and paraventricular nucleus of the hypothalamus (PVN) of mice 90 min following treatment with IP injected GDF15. Bottom: representative pictures of the staining ( n = 4 per group). Data are presented as mean ± s.e.m. with P values calculated using an unpaired two-tailed t test. Scale bar, 200 µm. 3V, third ventricle; ac, anterior commissure; BLA, basolateral amygdala; LV, lateral ventricle. f , Serum corticosterone following restraint (WT n = 9 mice, Gfral −/− n = 8) or the control condition (WT n = 9, Gfral −/− n = 8). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. g , Serum GDF15 after treatment with CRH (WT n = 5 mice, Gfral −/− n = 6) or vehicle (WT n = 3, Gfral −/− n = 4). Data are presented as mean ± s.e.m. with P values calculated using a two-way ANOVA with post hoc testing and Tukey’s correction. h , Schematic summary of the mechanism of GDF15-mediated anxiety-like behaviour. h created using BioRender.com .

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Saline, Control, Injection, Staining, Two Tailed Test

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a ) Non-ambulatory movements, b ) Total physical activity, c ) Total food intake, d ) respiratory exchange ratio (RER), e ) Energy expenditure in WT (saline n = 4 , epinephrine n = 4 ) and Gfral -/- mice (saline n = 4 , epinephrine n = 4 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA with post-hoc test and Tukey’s correction. f ) Chow intake (18-hrs) following tube restraint in WT (control n = 7 , restraint n = 7 ) and Gfral -/- mice (control n = 10 , restraint n = 9 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA. g ) Kaolin clay intake (18-hrs) following tube restraint in WT (control n = 7 , restraint n = 7 ) and Gfral -/- mice (control n = 10 , restraint n = 9 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA. h ) Time in center and total distance during open-field test following GDF15 treatment with representative images showing movement of individual mice. n = 9 per group. Data presented as mean ± s.e.m. with p-values calculated using unpaired two-tail t-test. i ) Time in light during light-dark box test following vehicle ( n = 8 ) or GDF15 treatment ( n = 9 ). Data presented as mean ± s.e.m. with p-values calculated using unpaired two-tail t-test. j ) Daily chow food intake throughout repeated GDF15 (5 nM/kg IP). n = 12 per group. Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA with post-hoc test and Tukey’s correction. k ) Time in the center during open-field test following GDF15 treatment (5 nM/kg IP) with representative images of movement of individual mice. n = 6 per group. Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA. Chr. GDF15: Chronic GDF15. l ) Total distance traveled during open-field test following GDF15 treatment (5 nM/kg IP) with representative images showing representative movement of individual mice. n = 6 per group. Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA. Chr. GDF15: Chronic GDF15.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Activity Assay, Saline, Control

Journal: Nature Metabolism

Article Title: GDF15 links adipose tissue lipolysis with anxiety

doi: 10.1038/s42255-025-01264-3

Figure Lengend Snippet: a ) Quantification of c-Fos positive cells in the locus coeruleus 90-min following GDF15 treatment (5 nm/kg IP), with representative pictures of the staining for TH and c-Fos. n = 4 per group. Data presented as mean ± s.e.m. with p-values calculated using unpaired two-tail t-test. Scale bar=200 µm. 4 V: 4 th ventricle, LC: locus coeruleus, TH: tyrosine hydroxylase. b ) Quantification of c-Fos positive cells in the PFC and BLA 90-min following GDF15 treatment (5 nm/kg IP), with representative pictures of the staining. n = 4 per group. Data presented as mean ± s.e.m. with p-values calculated using unpaired two-tail t-test. Scale bar=200 µm. BLA: basolateral amygdala, cc: corpus callosum, mPFC: medial prefrontal cortex. c ) Serum GDF15 in WT (control n = 9 , restraint n = 9 ) and Gfral -/- mice (control n = 8 , restraint n = 8 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA with Tukey’s post-hot correction. d ) Serum corticosterone in WT (control n = 4, CRH n = 6 ) and Gfral -/- mice (control n = 4 , CRH n = 6 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA at each timepoint. e ) Serum adrenocorticotropic hormone (ACTH) in WT (control n = 4, CRH n = 6 ) and Gfral -/- mice (control n = 4 , CRH n = 6 ). Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA at each timepoint. f ) Serum corticosterone 6-hr post treatment with dexamethasone (Dexa, 100 µg/kg IP). n = 4 per group. Data presented as mean ± s.e.m. with p-values calculated using 2-way ANOVA.

Article Snippet: Recombinant human GDF15 (5 nM kg −1 ; Novo Nordisk) or vehicle was injected IP at ~09:00 (ref. ).

Techniques: Staining, Control