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10.3390/ijms262311689
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Transcriptomic Changes Underlying the Anti-Steatotic Effects of DHA Supplementation in Aged Obese Female Mice

by
Álvaro Pejenaute Martínez de Lizarrondo
1,2,†,
Paula Martín-Climent
1,2,3,†,
María Martínez-Rubio
1,
Jesús Saborido-Gavilán
1,3,
Neira Sáinz
1,3,
Elisa Félix-Soriano
1,
Miriam Samblas
1,
Mónica Alfonso-Núñez
1,
Elizabeth Guruceaga
4,5,
M Pilar Lostao
1,2,3,4,
Pedro González-Muniesa
1,2,3,4 and
María J Moreno-Aliaga
1,2,3,4,*
1
Department of Nutrition, Food Science and Physiology and Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
2
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
3
Instituto de Nutrición y Salud (INS), University of Navarra, 31008 Pamplona, Spain
4
IdISNA—Navarra Institute for Health Research, 31008 Pamplona, Spain
5
Bioinformatics Platform, CIMA, University of Navarra, 31008 Pamplona, Spain
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(23), 11689; https://doi.org/10.3390/ijms262311689
Submission received: 30 May 2025 / Revised: 19 November 2025 / Accepted: 26 November 2025 / Published: 2 December 2025
(This article belongs to the Special Issue Cell Metabolism: Its Physiology, Dysfunction, and Related Metabolic Complications)
Versions Notes

Abstract

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.
Keywords: obesity; docosahexaenoic acid; metabolic dysfunction-associated steatotic liver disease; lipid metabolism obesity; docosahexaenoic acid; metabolic dysfunction-associated steatotic liver disease; lipid metabolism

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MDPI and ACS Style

Pejenaute Martínez de Lizarrondo, Á.; Martín-Climent, P.; Martínez-Rubio, M.; Saborido-Gavilán, J.; Sáinz, N.; Félix-Soriano, E.; Samblas, M.; Alfonso-Núñez, M.; Guruceaga, E.; Lostao, M.P.; et al. Transcriptomic Changes Underlying the Anti-Steatotic Effects of DHA Supplementation in Aged Obese Female Mice. Int. J. Mol. Sci. 2025, 26, 11689. https://doi.org/10.3390/ijms262311689

AMA Style

Pejenaute Martínez de Lizarrondo Á, Martín-Climent P, Martínez-Rubio M, Saborido-Gavilán J, Sáinz N, Félix-Soriano E, Samblas M, Alfonso-Núñez M, Guruceaga E, Lostao MP, et al. Transcriptomic Changes Underlying the Anti-Steatotic Effects of DHA Supplementation in Aged Obese Female Mice. International Journal of Molecular Sciences. 2025; 26(23):11689. https://doi.org/10.3390/ijms262311689

Chicago/Turabian Style

Pejenaute Martínez de Lizarrondo, Álvaro, Paula Martín-Climent, María Martínez-Rubio, Jesús Saborido-Gavilán, Neira Sáinz, Elisa Félix-Soriano, Miriam Samblas, Mónica Alfonso-Núñez, Elizabeth Guruceaga, M Pilar Lostao, and et al. 2025. "Transcriptomic Changes Underlying the Anti-Steatotic Effects of DHA Supplementation in Aged Obese Female Mice" International Journal of Molecular Sciences 26, no. 23: 11689. https://doi.org/10.3390/ijms262311689

APA Style

Pejenaute Martínez de Lizarrondo, Á., Martín-Climent, P., Martínez-Rubio, M., Saborido-Gavilán, J., Sáinz, N., Félix-Soriano, E., Samblas, M., Alfonso-Núñez, M., Guruceaga, E., Lostao, M. P., González-Muniesa, P., & Moreno-Aliaga, M. J. (2025). Transcriptomic Changes Underlying the Anti-Steatotic Effects of DHA Supplementation in Aged Obese Female Mice. International Journal of Molecular Sciences, 26(23), 11689. https://doi.org/10.3390/ijms262311689

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