Contrasting Effects of Western vs. Mediterranean Diets on Monocyte Inflammatory Gene Expression and Social Behavior in a Primate Model

Abstract

23Summary 24Monocytes and macrophages-important mediators of innate immunity, health, and disease-are 25 sensitive to diet and stress. Western diets promote inflammation and disease, while 26Mediterranean diets reduce inflammation and promote health, although the mechanisms through 27 which diet alters immune function are unknown. Here, we conducted the first randomized, long-28 term diet trial in which macaques were fed either a Western-or Mediterranean-like diet to 29 determine how diet and behavior interact to influence monocyte polarization-a precursor to 30 subsequent health outcomes. Monocyte gene expression profiles differed markedly between the 31 two diets, with over 40% of expressed genes being differentially expressed (FDR<0.05). The 32Western diet induced a more proinflammatory monocyte phenotype with changes in monocyte 33 polarization-associated genes. Diet also shifted the co-expression of gene pairs, including small 34RNAs and transcription factors that are associated with metabolism and adiposity in humans. We 35 also found that diet altered a suite of affiliative and anxiety-associated behaviors, and these 36 behavioral changes mediated ~20% of the effect of diet on monocyte gene expression. Together, 37 these findings suggest that diet-induced effects on monocyte polarization are due, in part, to both 38 direct and behaviorally-mediated effects on monocyte gene expression. 39

Diet, psychosocial stress, and Alzheimer’s disease-related neuroanatomy in female nonhuman primates

“…The biological mechanisms underlying increased GM volume and cortical thickening require further study; however, they may reflect neuroinflammatory responses, as increases in GM volumes [49] and cortical thickening [50] have been associated with neuroinflammation in recent clinical studies. Western diets are pro-inflammatory [11,51], and we previously reported that circulating monocytes isolated from the Western group had pro-inflammatory gene expression profiles relative to those from the Mediterranean group [52]. We also reported that the Western group had lower rates of affiliation and social integration and higher rates of anxiety and social isolation than the Mediterranean group, suggesting that diet impacted the brain [52].…”

“…Western diets are pro-inflammatory [11,51], and we previously reported that circulating monocytes isolated from the Western group had pro-inflammatory gene expression profiles relative to those from the Mediterranean group [52]. We also reported that the Western group had lower rates of affiliation and social integration and higher rates of anxiety and social isolation than the Mediterranean group, suggesting that diet impacted the brain [52]. Importantly, social isolation and anxiety are risk factors for dementia [53].…”