Contrasting effects of Western vs Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model

eLife

Timothy D Howard¹  Gregory A Hawkins¹  Edward H Ip²  Charles E McCall³  David M Herrington⁴  Kristofer T Michalson⁵  Susan E Appt⁵  Thomas C Register⁵  Ryne J DeBo⁵  Carol Shively⁵  Corbin SC Johnson⁶  Noah Snyder-Mackler⁷  Yongmei Liu⁸  Amanda J Lea⁹ 

[1] Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, United States;Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, United States;Department of Internal Medicine, Section of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, United States;Department of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, United States;Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, United States;Department of Psychology, University of Washington, Seattle, United States;Department of Psychology, University of Washington, Seattle, United States;Center for Studies in Demography and Ecology, University of Washington, Seattle, United States;Department of Biology, University of Washington, Seattle, United States;School of Life Sciences, Arizona State University, Tempe, United States;Center for Evolution & Medicine, Arizona State University, Tempe, United States;Division of Cardiology, Duke University School of Medicine, Durham, United States;Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States;Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States;

关键词: Macaca fascicularis;    evolutionary mismatch;    diet;    monocyte;    behavior;    gene regulation;    Other;   

DOI  :  10.7554/eLife.68293

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Dietary changes associated with industrialization increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease. This relationship is often attributed to an ‘evolutionary mismatch’ between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout human evolutionary history (e.g. simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to ancestral human hunter-gatherer diets, such as a Mediterranean diet. Peripheral blood monocytes, precursors to macrophages and important mediators of innate immunity and inflammation, are sensitive to the environment and may represent a critical intermediate in the pathway linking diet to disease. We evaluated the effects of 15 months of whole diet manipulations mimicking Western or Mediterranean diet patterns on monocyte polarization in a well-established model of human health, the cynomolgus macaque (Macaca fascicularis). Monocyte transcriptional profiles differed markedly between diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. The Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered behavior. For example, Western-fed individuals were more anxious and less socially integrated. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. This study provides new molecular insights into an evolutionary mismatch and uncovers new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.

【 授权许可】

CC BY