PXD083028

PXD083028 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-22 21:57:56	ID requested
⏵ 1	2026-08-25 01:03:42	announced

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;

submitter keyword: mouse, proteomics, DIA, plasma

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

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PRIDE project URI

• PRIDE
  1. PXD083028
     1. Label: PRIDE project
     2. Name: GDF15 Resolves Liver Inflammation in MASH Independently of Reductions in Food Intake or Weight Loss