Monocyte transcriptomic profile following EPA and DHA supplementation in men and women with low-grade chronic inflammation

Authors: SO, JISUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; TAI, ALBERT - Tufts University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/29/2023
Publication Date: 1/1/2024
Citation: So, J., Wu, D., Tai, A.K., Lichtenstein, A.H., Matthan, N., Lamon-Fava, S. 2024. Monocyte transcriptomic profile following EPA and DHA supplementation in men and women with low-grade chronic inflammation. Atherosclerosis. https://doi.org/10.1016/j.atherosclerosis.2023.117407.
DOI: https://doi.org/10.1016/j.atherosclerosis.2023.117407

Interpretive Summary: Cardiovascular disease is the leading cause of death in the United States. Intake of fish and fish oil, which contain relatively high amounts of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been associated with lower cardiovascular disease risk. It is yet unknown if EPA and DHA have similar biological effects and, if so, the effects are sex specific. To address this question, we supplemented women and men with EPA and DHA for 10-week periods each. At the end of the supplementation period, we isolated white blood cells and determined the resulting gene expression effects. We found that EPA and DHA supplementation elicited both similar and different effects, some of which were sex specific. These data expand our understanding of the effects of EPA and DHA, and the resulting sex specific differences.

Technical Abstract: Background: Fish oil supplementation studies have reported mixed results on cardiovascular disease risk. Inconsistency in results may be due to differences in the relative amount of supplemental EPA and DHA in these studies and the potential differential effect of EPA and DHA on immune functions and inflammation. Methods: Eight men and 8 postmenopausal women (50-75 y) with low-grade chronic inflammation were enrolled in a randomized, crossover study comparing 3 g/d EPA, 3 g/d DHA, and control (3 g/d high oleic acid sunflower oil). Blood monocytes were isolated at the end of each phase for RNA-seq. Results: Sex dimorphism in monocyte gene expression was observed within each phase of the study, therefore data for women and men were analyzed separately. In men, 1,088 genes were differentially expressed (p <0.05) in response to EPA or DHA supplementation. In men, relative to baseline, both EPA and DHA supplementation repressed biological processes involved in energy metabolism and cellular stress response, and upregulated PPARalpha activation. In women, 997 genes were differentially expressed, and EPA and DHA inhibited processes involved in mitochondrial energy metabolism and upregulated biological processes involved in stress response. Relative to DHA, EPA resulted in lower expression of genes involved in inflammatory processes in men, and lower expression of genes involved in endoplasmic reticulum stress response in women. Conclusions: EPA and DHA elicited both similar and differential effects on monocyte transcriptome. Of interest was the observed difference in response to EPA and DHA supplementation in men and women, suggesting sex-dependent innate immune responses.