Introduction: Insomnia symptoms are prevalent in Hispanic/Latino adults, and insomnia is a risk factor for cardiometabolic disease, possibly through dysregulated inflammatory pathways. However, existing evidence has largely focused on non-specific and downstream inflammatory biomarkers. Informed by prior research, we hypothesized that insomnia promotes chronic low-grade inflammation by disrupting the physiological balance between upstream bioactive fatty acids and oxylipins. Objective: To evaluate associations between insomnia and 81 upstream bioactive fatty acid and oxylipin inflammatory biomarkers in the population-based Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: After excluding night and rotating shift workers, participants were 14,439 HCHS/SOL adults (mean age: 46 y, 61% female, 62% with education ≥ high school degree). Insomnia was measured using the Women’s Health Initiative Insomnia Rating Scale (WHIIRS). We used the WHIIRS score as a continuous (range 0-20, with higher scores indicating greater severity) and categorical variable (WHIIRS ≥ 9, indicating clinically significant insomnia). The 81 oxylipins and fatty acids were profiled in fasting blood samples using non-targeted liquid chromatography-mass spectrometry and annotated based on mass-to-charge ratio, retention time, and spectra. Cross-sectional associations between rank normalized oxylipins and fatty acids with insomnia were assessed using survey-weighted multivariable linear regression adjusting for confounders (age, sex, center, Hispanic background group, education, smoking, alcohol use, the alternative healthy eating index, physical activity, and body mass index). We addressed multiple comparisons using a false discovery rate <0.05. Results: The mean WHIIRS score was 7.1 (standard deviation: 5.4) and 36% displayed clinically significant insomnia. The WHIIRS showed statistically significant positive associations with 7 fatty acids (nervonic, docosadienoic, palmitoleic, eicosanoic, docosaenoic, behenic, and lignoceric acid) and 4 oxylipins (HpODE, leukotriene/HpETE/DiHETE/prostaglandin, HOTrE/oxoODE, and an oxylipin with unknown biological pathway). Clinically significant insomnia defined categorically showed statistically significant positive associations with 3 fatty acids and 3 oxylipins, all of which were also identified in the continuous WHIIRS analysis (see above). Identified fatty acids and oxylipins included both putative pro-inflammatory (e.g., HpODE) and anti-inflammatory (e.g., nervonic acid) compounds. Conclusions: Insomnia, like cardiometabolic disease, is associated with low-grade inflammation. The directionality of these relationships and degree to which associations between chronic inflammation with cardiometabolic disease and insomnia reflects overlapping pathways warrants further investigation.
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