Summary
Monocytes and macrophages—important mediators of innate immunity, health, and disease—are sensitive to diet and stress. Western diets promote inflammation and disease, while Mediterranean diets reduce inflammation and promote health, although the mechanisms through which diet alters immune function are unknown. Here, we conducted the first randomized, long-term diet trial in which macaques were fed either a Western- or Mediterranean-like diet to determine how diet and behavior interact to influence monocyte polarization–a precursor to subsequent health outcomes. Monocyte gene expression profiles differed markedly between the two diets, with over 40% of expressed genes being differentially expressed (FDR<0.05). The Western diet induced a more proinflammatory monocyte phenotype with changes in monocyte polarization-associated genes. Diet also shifted the co-expression of gene pairs, including small RNAs and transcription factors that are associated with metabolism and adiposity in humans. We also found that diet altered a suite of affiliative and anxiety-associated behaviors, and these behavioral changes mediated ∼20% of the effect of diet on monocyte gene expression. Together, these findings suggest that diet-induced effects on monocyte polarization are due, in part, to both direct and behaviorally-mediated effects on monocyte gene expression.
