| Title: |
Perinatal obesity primes the hepatic metabolic stress response in the offspring across life span |
| Authors: |
Stegmann, Sarah K.; Vohlen, Christina; Im, Nam Gyu; Niehues, Jana; Selle, Jaco; Janoschek, Ruth; Kuiper-Makris, Celien; Lang, Sonja; Demir, Münevver; Steffen, Hans-Michael; Quaas, Alexander; Lackmann, Jan-Wilm; Nierhoff, Dirk; Neumann-Haefelin, Christoph; Dötsch, Jörg; Alejandre Alcazar, Miguel A.; Kasper, Philipp |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2025 |
| Collection: |
Cologne University: KUPS |
| Subject Terms: |
Medical sciences Medicine |
| Description: |
[Article number: 6416] Perinatal obesity is associated with an increased risk of metabolic diseases and hepatic dysfunction in offspring. However, the underlying mechanisms of this metabolic programming remain incompletely understood. This study aimed to elucidate the influence of maternal obesity and early life exposure to high-fat diet on offspring liver phenotype, hepatokine profile, and key components of hepatic metabolism. To this end, we employed a murine high-fat diet-induced perinatal obesity model, investigating the offspring in early life and late adulthood. After exposure to perinatal obesity, the offspring showed a significantly increased body weight in early life with no histological signs of steatosis, but a dysregulated hepatokine profile. Proteomic profiling, followed by molecular analyses, revealed a decreased lipogenesis and increased fatty acid oxidation, suggesting a protective mechanism against the development of steatosis. These changes were accompanied by increased markers of lipid peroxidation and DNA damage, indicating increased oxidative stress. Concomitantly, the antioxidative enzymes catalase and superoxide dismutase 2 were significantly reduced and oxidative phosphorylation was impaired, implying an altered oxidative stress response. While changes in oxidative stress level were only detected in early life, the lipid metabolism was altered across life span. This metabolic programming could determine the resilience and susceptibility to chronic liver disease later in life. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
German; English |
| ISSN: |
2045-2322 |
| Relation: |
http://kups.ub.uni-koeln.de/79297/1/s00018-025-05635-7.pdf; Stegmann, Sarah K. orcid:0000-0002-3366-3906 , Vohlen, Christina orcid:0000-0002-6395-7999 , Im, Nam Gyu orcid:0000-0002-8839-7692 , Niehues, Jana orcid:0000-0001-5996-8292 , Selle, Jaco orcid:0000-0002-4981-0931 , Janoschek, Ruth orcid:0000-0002-1332-9353 , Kuiper-Makris, Celien orcid:0000-0002-7940-9612 , Lang, Sonja orcid:0000-0001-5710-6103 , Demir, Münevver orcid:0000-0002-7050-797X , Steffen, Hans-Michael orcid:0000-0001-6562-3549 , Quaas, Alexander orcid:0000-0002-3537-6011 , Lackmann, Jan-Wilm orcid:0000-0001-8182-8034 , Nierhoff, Dirk orcid:0000-0001-7297-2675 , Neumann-Haefelin, Christoph orcid:0000-0001-7351-1387 , Dötsch, Jörg orcid:0000-0003-1529-7647 , Alejandre Alcazar, Miguel A. orcid:0000-0002-3176-0411 and Kasper, Philipp orcid:0000-0002-6218-2239 (2025). Perinatal obesity primes the hepatic metabolic stress response in the offspring across life span. Scientific Reports, 15. pp. 1-13. Springer Nature. ISSN 2045-2322 |
| DOI: |
10.1038/s41598-025-90082-4 |
| Availability: |
http://kups.ub.uni-koeln.de/79297/; https://doi.org/10.1038/s41598-025-90082-4 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.9C38017B |
| Database: |
BASE |