Contrasting effects of Western vs. Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model
- University of Washington, United States
- Wake Forest School of Medicine, United States
- Princeton University, United States
- Duke University School of Medicine, United States
- Arizona State University, United States
Abstract
Dietary changes associated with industrialization substantially increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease, major contributors to the public health burden. The high prevalence of these chronic diseases 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 human Western or Mediterranean diet patterns on monocyte polarization using a well-established model of human health, the cynomolgus macaque (Macaca fascicularis). Monocyte transcriptional profiles differed markedly between the two diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. Compared to the Mediterranean diet, 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 compared to the Mediterranean-fed subjects. 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. The results of this study provide new insights into evolutionary mismatch at the molecular level and uncover new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.
Data availability
Sequencing data have been deposited in GEO under accession code GSE144314.Code can be found here: https://github.com/cscjohns/diet_behavior_immunity
Article and author information
Author details
Noah Snyder-Mackler
Funding
National Heart, Lung, and Blood Institute (R01HL087103)
- Carol Shively
National Heart, Lung, and Blood Institute (R01HL122393)
- Carol Shively
- Thomas C Register
National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097748)
- Thomas C Register
National Institute on Aging (R00AG051764)
- Noah Snyder-Mackler
National Institute on Aging (R01AG060931)
- Noah Snyder-Mackler
Wake Forest School of Medicine
- Carol Shively
Helen Hay Whitney Foundation
- Amanda J Lea
National Cancer Institute (P30CA012197)
- Carol Shively
- Timothy D Howard
- Gregory A Hawkins
- Susan E Appt
- Charles E McCall
- David M Herrington
- Edward H Ip
- Thomas C Register
National Institutes of Health (S10OD023409)
- Gregory A Hawkins
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal manipulations were performed according to the guidelines of state and federal laws, the US Department of Health and Human Services, and the Animal Care and Use Committee of Wake Forest School of Medicine (ACUC #A12-195; #A15-180).
Copyright
© 2021, Johnson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Contrasting effects of Western vs. Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model
eLife 10:e68293.
https://doi.org/10.7554/eLife.68293
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- Evolutionary Biology
- Epidemiology and Global Health
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