1. Epidemiology and Global Health
  2. Immunology and Inflammation

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

  1. Corbin SC Johnson
  2. Carol A Shively
  3. Kristofer T Michalson
  4. Amanda J Lea
  5. Ryne J DeBo
  6. Timothy D Howard
  7. Gregory A Hawkins
  8. Susan E Appt
  9. Yongmei Liu
  10. Charles E McCall
  11. David M Herrington
  12. Edward H Ip
  13. Thomas C Register  Is a corresponding author
  14. Noah Snyder-Mackler  Is a corresponding author
  1. Department of Psychology, University of Washington, United States
  2. Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, United States
  3. Lewis-Sigler Institute for Integrative Genomics, Princeton University, United States
  4. Department of Ecology and Evolutionary Biology, Princeton University, United States
  5. Department of Biochemistry, Wake Forest School of Medicine, United States
  6. Division of Cardiology, Duke University School of Medicine, United States
  7. Department of Internal Medicine, Section of Molecular Medicine, Wake Forest School of Medicine, United States
  8. Department of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest School of Medicine, United States
  9. Department of Biostatistics and Data Science, Wake Forest School of Medicine, United States
  10. Center for Studies in Demography and Ecology, University of Washington, United States
  11. Department of Biology, University of Washington, United States
  12. School of Life Sciences, Arizona State University, United States
  13. Center for Evolution & Medicine, Arizona State University, United States
https://doi.org/10.7554/eLife.68293
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Cite this article
  1. Corbin SC Johnson
  2. Carol A Shively
  3. Kristofer T Michalson
  4. Amanda J Lea
  5. Ryne J DeBo
  6. Timothy D Howard
  7. Gregory A Hawkins
  8. Susan E Appt
  9. Yongmei Liu
  10. Charles E McCall
  11. David M Herrington
  12. Edward H Ip
  13. Thomas C Register
  14. Noah Snyder-Mackler
(2021)
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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8 figures, 1 table and 2 additional files

Figures

Figure 1 with 2 supplements
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Diet effects on monocyte gene expression.

(A) Diet was significantly associated with the first principal component of gene expression (59% variance explained, t(25.1) = 4.4, p = 1.72 x 10−4). (B) The average effect size of diet on Western …

Figure 1—figure supplement 1
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Genes with significantly higher expression in monkeys fed the Western diet (‘Western genes’) were enriched for genes associated with numerous complex human diseases and traits.
Figure 1—figure supplement 2
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Expression of genes in the conserved transcriptional response to adversity (CTRA Cole et al., 2015) indicate inflammatory effects of a Western diet that parallel the effects of social adversity.
Figure 2
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Transcription factor (TF) binding motifs correlated with diet effects on gene expression.

The log-odds ratio of TF binding motif enrichment in Western genes (orange) or Mediterranean genes (blue) are depicted on the x-axis. The y-axis shows the effect size of diet on the expression of …

Figure 3
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Diet altered monocyte gene co-expression.

(A) The Pearson correlation between each pair of genes within each of the experimental diets. Gene pairs that were significantly differently correlated between diets are highlighted in blue (n = 445 …

Figure 4 with 2 supplements
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Diet alters behavioral phenotype.

(A) Three behaviors were significantly different between the two diet groups. Monkeys fed the Mediterranean diet spent more time in body contact (Holm-Bonferroni adjusted p (pHB) = 1.1 x 10−5) and …

Figure 4—figure supplement 1
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Diet manipulation altered behavior.
Figure 4—figure supplement 2
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The first PC of all behavioral data captures dominance rank.
Figure 5
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Behavior partially mediates the effect of diet on gene expression for 24% of diet-associated genes.

(A) Diet-altered behavior (DAB) mediated the effect of diet on gene expression for 24% (n = 1199) of genes for which diet had an effect (differentially expressed genes or DEGs). For 18% of DEGs, …

Appendix 1—figure 1
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RNA Integrity was correlated with both uncorrected gene expression and relative rank.

(A) RNA integrity (RIN) was correlated with PC1 of gene expression (62% of overall variance in gene expression) prior to correction for batch effects (Pearson’s r = 0.41, p = 0.020). Because of …

Appendix 2—figure 1
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Greater phenotypic variability in Western diet fed monkeys does not show consistency in individual responsiveness across phenotypes.

(A) Monkeys fed the Western diet showed more variability than monkeys fed the Mediterranean diet in both diet-altered behavior (DAB) and change in body weight. However, the two phenotypes were not …

Appendix 2—figure 2
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Quality control of cell purity by CD14 and CD3 expression levels: three samples were excluded due to lower CD14 and high CD3 – possible T cell contamination.

Normalized expression (reads per kilobase million) of CD14 and CD3 are plotted as markers of monocytes and T cells, respectively. Three samples were excluded as outliers due to possible T cell …

Tables

Table 1
Comparison of nutritional contents of diet patterns in human with nonhuman primate diets used in the current study.
Diet CompositionHumanNonhuman Primate
WesternMediterraneanWestern*Mediterranean*Chow†
% of Calories
Protein15§1716§1618
Carbohydrate‡51§5154§5469
Fat33§3231§3113
% of Total fats
Saturated33§2136§2126
Monounsaturated36§5636§5728
Polyunsaturated24§1526§2032
Other nutrients
ω6:ω3 Fatty Acids15:1††2.1-3:1‡‡14.8:1††2.9:1‡‡12:01
Cholesterol mg/Cal0.13§0.160.16§0.15trace
Fiber g/Cal0.01§0.03§§0.02§0.04§§0.01
Sodium mg/Cal1.7§,¶¶1.3¶,§§1.7§,¶¶1.1¶,§§0.25

  1. * Developed and prepared at Wake Forest School of Medicine.

    † LabDiet Chemical Composition Diet 5037/8. Type of fat known in 86% of total fat. Omega-6 from corn and pork fat.

  2. ‡ Human carbohydrate calories include alcohol.

    §(Centers for Disease Control and Prevention (CDC), 2014).

  3.  (Bédard et al., 2012).

    †† (Simopoulos, 2006).

  4. ‡‡ (Cordain et al., 2005).

    §§ (Kafatos et al., 2000).

  5. ¶¶ (Powles et al., 2013).

    Reprinted from Shively et al., 2019, Obesity with permission (Shively et al., 2019).

Additional files

Supplementary file 1

Supplementary tables 1-6.

Suppl.tab 1A Effect of diet on gene expression. Suppl.tab 1B Effects of diet on gene expression (FDR < 0.05 β sort). Suppl.tab 2A Biological processes enriched in western genes compared to other measured genes Suppl.tab 2B. Biological processes enriched in mediterranean genes compared to other measured genes. Suppl.tab 3. Transcription factor binding site motif enrichment. Suppl.tab 4A. Diet correlation and gene set enrichment of weighted gene co-expression network analysis (WGCNA) co-expression modules. Suppl.tab 4B. Biological processes enriched in WGCNA co-expression modules. Suppl.tab 5A. Gene pair correlations across and within diet groups. Suppl.tab 5B. Differentially Correlated Genes. Suppl.tab 6A. Biological processes enriched in behavior-mediated differentially-expressed genes (DEGs) Suppl.tab 6B. Biological processes enriched in behavior-mediated western genes Suppl.tab 6C. Biological processes enriched in behavior-mediated mediterranean genes.

https://cdn.elifesciences.org/articles/68293/elife-68293-supp1-v3.xlsx
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