Transcriptomic Changes Underlying the Anti-Steatotic Effects of DHA Supplementation in Aged Obese Female Mice
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) increases with age and obesity. The aim of this study was to characterize the transcriptomic changes in liver underlying the beneficial effects of docosahexaenoic acid (DHA) supplementation on MASLD progression in aged obese female mice. Two-month-old C57BL/6J female mice were fed ad libitum with high fat saturated diet (HFD, 45%) for 4 months. These diet-induced obese (DIO) mice were divided into two groups: the DIO group that continued with HFD and the DIO + DHA mice fed up to 18 months with the HFD containing a DHA-rich concentrate. High quality RNA from liver was used to perform RNA sequencing analysis. Further functional and clustering analyses of differentially expressed genes (DEGs) in liver between treatments revealed that DHA regulated processes related to lipid metabolic processes. DHA treatment also affects the PPAR signaling pathway and the regulation of inflammatory response. These data suggest that long-term DHA supplementation ameliorates MASLD progression in aged obese female mice by promoting transcriptomic changes in genes related to lipid metabolism and inflammatory response.
Authors
- María J. Moreno‐Aliaga (ORCID: https://orcid.org/0000-0002-2018-6434)
- Paula Martín-Climent (ORCID: https://orcid.org/0000-0001-8501-3983)
- Mónica Alfonso-Núñez (ORCID: https://orcid.org/0000-0002-5355-0423)
- María V Martínez-Rubio
- Elizabeth Guruceaga (ORCID: https://orcid.org/0000-0003-0547-681X)
- M. Pilar Lostao (ORCID: https://orcid.org/0000-0002-7319-3451)
- Neira Sáinź (ORCID: https://orcid.org/0000-0003-0298-3031)
- Álvaro Pejenaute (ORCID: https://orcid.org/0000-0002-0260-7848)
- Elisa Félix‐Soriano (ORCID: https://orcid.org/0000-0003-4633-1289)
- Pedro González‐Muniesa (ORCID: https://orcid.org/0000-0002-3130-2496)
- Mirian Samblas (ORCID: https://orcid.org/0000-0003-0866-2300)
- Jesús Saborido-Gavilán (ORCID: https://orcid.org/0009-0009-8177-7754)
Institutions
- Instituto de Salud Carlos III (ES)
- Instituto de Salud Pública de Navarra (ES)
- Navarre Institute of Health Research (ES)
- Centro de Investigación Biomédica en Red (ES)
- Universidad de Navarra (ES)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-12-02
- DOI
- https://doi.org/10.3390/ijms262311689
- Primary Topic
- Fatty Acid Research and Health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Universidad de Navarra
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Gobierno de Navarra
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación