PXD083028 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | GDF15 Resolves Liver Inflammation in MASH Independently of Reductions in Food Intake or Weight Loss |
| Description | Growth differentiation factor 15 (GDF15) is strongly associated with metabolic dysfunction-associated steatohepatitis (MASH), yet whether it drives disease or protects against liver injury remains unresolved. Using thermoneutral mouse models that closely mimic human MASH, we show that loss of GDF15 or its receptor GFRAL selectively worsens hepatic inflammation and fibrosis independently of steatosis or insulin resistance. Conversely, recombinant GDF15 suppressed liver inflammation and fibrosis more effectively than matched caloric restriction despite equivalent reductions in food intake, body weight, and steatosis. Spatial transcriptomics and bulk RNA-seq revealed that GDF15 remodels the hepatic immune-fibrotic niche by suppressing pro-inflammatory macrophages, plasma B cells, and activated stellate cells while promoting pro-resolving immune programs. These effects required GFRAL but occurred independently of β-adrenergic signaling. In a steatosis-free CCl₄ model, GDF15 retained potent anti-inflammatory effects and activated hypothalamic-pituitary-adrenal (HPA) axis and hepatic glucocorticoid receptor (GR) signaling, which were blunted by GR antagonism. Together, these findings identify GDF15 as an endogenous neuroimmune regulator that restrains liver inflammation and fibrosis independently of weight loss or steatosis through a GFRAL–HPA–GR signaling axis. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-08-25 |
| AnnouncementXML | Submission_2026-08-25_01:03:41.589.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Annabelle Hoegl |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | Q Exactive HF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-08-22 21:57:56 | ID requested | |
| ⏵ 1 | 2026-08-25 01:03:42 | announced | |
Publication List
| 10.1016/j.cmet.2026.07.008; |
| Wang D, Jabile MJT, Di Pastena F, Townsend LK, Ahmadi E, Hoegl A, Payne A, Lavoie DCT, Batchuluun B, Gautam J, Morrow MR, Lally JSV, Kuhre RE, J, ø, rgensen SB, Steinberg GR, GDF15 suppresses liver inflammation independently of weight loss through neuroendocrine glucocorticoid signaling. Cell Metab, ():(2026) [pubmed] |
| 10.1016/J.CMET.2026.07.008; |
Keyword List
| submitter keyword: mouse, proteomics, DIA, plasma |
Contact List
| Annabelle Hoegl |
|---|
| contact affiliation | Biomarker Assay Development 1 Novo Nordisk Park 1 Måløv, Denmark |
| contact email | yabh@novonordisk.com |
| lab head | |
| Annabelle Hoegl |
|---|
| contact affiliation | Novo Nordisk A/S |
| contact email | yabh@novonordisk.com |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD083028
- Label: PRIDE project
- Name: GDF15 Resolves Liver Inflammation in MASH Independently of Reductions in Food Intake or Weight Loss
