PXD058285-1

PXD058285 is an original dataset announced via ProteomeXchange.

Title	Developmental programming of Kupffer cells by maternal obesity causes fatty liver disease in the offspring
Description	Kupffer cells (KCs) are tissue-resident macrophages which colonize the liver early during embryogenesis. KCs start to acquire a tissue-specific transcriptional signature immediately after colonizing the liver, mature together with the tissue, and adapt to the tissue?s functions. Throughout development and adulthood, KCs have distinct core functions that are essential for liver and organismal homeostasis, such as supporting fetal erythropoiesis as well as postnatal erythrocyte recycling and liver metabolism. However, whether perturbations of macrophage core functions during development contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a mouse model of maternal obesity to perturb KC functions during gestation. We show that offspring exposed to maternal obesity develop fatty liver disease, driven by aberrant developmental programming of KCs that persists into adulthood. Programmed KCs mediate lipid uptake by hepatocytes through apolipoprotein secretion. KC depletion in neonates born to obese mothers, followed by replenishment with exogenous monocytes, rescues the fatty liver disease. The transcriptional programming of KCs and the fatty liver disease phenotype are also rescued by genetic depletion of hypoxia-inducible factor alpha (Hif1?) in macrophages during gestation. These results establish developmental perturbation of KC functions as a cause for the development of fatty liver disease in adult life and, thereby, place fetal-derived macrophages as intergenerational messengers within the concept of developmental origins of health and diseases.
HostingRepository	PRIDE
AnnounceDate	2025-09-01
AnnouncementXML	Submission_2025-08-31_17:40:38.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Diana Fink
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-26 04:40:08	ID requested
⏵ 1	2025-08-31 17:40:39	announced

10.1038/s41586-025-09190-w;

Huang H, Balzer NR, Seep L, Splichalova I, Blank-Stein N, Viola MF, Franco Taveras E, Acil K, Fink D, Petrovic F, Makdissi N, Bayar S, Mauel K, Radwaniak C, Zurkovic J, Kayvanjoo AH, Wunderling K, Jessen M, Yaghmour MH, Kenner L, Ulas T, Grein S, Schultze JL, Scott CL, Guilliams M, Liu Z, Ginhoux F, Beyer MD, Thiele C, Meissner F, Hasenauer J, Wachten D, Mass E, Kupffer cell programming by maternal obesity triggers fatty liver disease. Nature, 644(8077):790-798(2025) [pubmed]

submitter keyword: kupffer cells,fatty liver, mouse, maternal obesity

Elvira Mass
contact affiliation	Developmental Biology of the Immune System, Life & Medical Sciences (LIMES) Institute,University of Bonn; 53115 Bonn, Germany
contact email	diana.fink@uni-bonn.de
lab head
Diana Fink
contact affiliation	Institute of Innate Immunity Bonn
contact email	diana.fink@uni-bonn.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058285
     1. Label: PRIDE project
     2. Name: Developmental programming of Kupffer cells by maternal obesity causes fatty liver disease in the offspring