DHA or EPA after weaning reduced depressive-like behavior and restored some myelin measures in maternal high-fat-diet rat offspring

In a rat study, offspring exposed to a maternal high-fat diet during pregnancy and lactation showed reduced forced-swim immobility after receiving docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)-enriched diets following weaning, according to the study abstract. Both diets also partially restored measures related to myelin in the prefrontal cortex, with EPA producing broader molecular and cellular changes than DHA. These findings come from an animal experiment and do not establish a treatment effect in people.

Researchers fed maternal rats a diet containing 60% of energy from fat during pregnancy and lactation. After weaning, offspring received DHA- or EPA-enriched diets until adulthood. Depressive-like behavior was evaluated with the forced swimming test, while myelin-related changes were examined using RT-qPCR, ELISA and immunofluorescence staining. The abstract reports that both supplemented diets normalized the increased immobility time recorded in adult offspring exposed to the maternal high-fat diet, relative to offspring receiving standard diet after weaning.

The molecular responses differed by sex. In male offspring, DHA and EPA normalized messenger RNA levels for myelin-oligodendrocyte glycoprotein (MOG), 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) and transferrin. Only EPA additionally restored messenger RNA levels for myelin and lymphocyte protein (MAL) and kallikrein 6 (KLK6). At the protein level, DHA normalized MOG, whereas EPA restored MOG, MAL and CNPase. In females, both supplements increased Mog messenger RNA, while DHA also increased Klk6 messenger RNA compared with the maternal high-fat-diet and post-weaning standard-diet group. Immunofluorescence results also differed by sex, with broader restoration of oligodendrocytes and myelin intensity in males.

Maternal high-fat diet exposure reduced brain-derived neurotrophic factor levels in male offspring at both messenger RNA and protein levels, while post-weaning DHA and EPA restored Bdnf messenger RNA expression. Overall, the abstract reports that both supplements alleviated forced-swim-assessed depressive-like behavior and partially restored prefrontal-cortex myelin abnormalities. The restoration was incomplete and varied by sex, marker and supplement. Because the experiment involved rats and measured behavior with a single test, the results should be interpreted as preclinical evidence rather than evidence of clinical benefit, and the abstract does not establish that either supplement can reverse broader effects of early-life dietary exposure in humans.

Subject of Research: Post-weaning DHA and EPA supplementation in a rat model of maternal high-fat-diet exposure

Article Title: Post-weaning DHA or EPA supplementation attenuates depressive-like behavior and myelination deficits induced by maternal high-fat diet in rat offspring

Article References: Śliwa, M., Frankowska, M., Jastrzębska, J., Wesołowska, J., Filip, M., & Smaga, I. (2026). Post-weaning DHA or EPA supplementation attenuates depressive-like behavior and myelination deficits induced by maternal high-fat diet in rat offspring. Scientific Reports. https://doi.org/10.1038/s41598-026-75094-y

Image Credits: AI Generated

DOI: 10.1038/s41598-026-75094-y

Keywords: DHA, EPA, maternal high-fat diet, rat offspring, depressive-like behavior, forced swimming test, prefrontal cortex, myelin, BDNF, Post-weaning, supplementation, attenuates