Abstract

Data on proteomic and metabolomic signatures of healthy dietary patterns are limited. We evaluated the cross-sectional association of serum proteomic and metabolomic markers with three dietary patterns: the Alternative Healthy Eating Index (AHEI), the Dietary Approaches to Stop Hypertension (DASH) diet; and a Mediterranean-style (MDS) diet. We examined participants from the Framingham Offspring Study (mean age; 55 years; 52% women) who had complete proteomic (n = 1713) and metabolomic (n = 2284) data; using food frequency questionnaires to derive dietary pattern indices. Proteins and metabolites were quantified using the SomaScan platform and liquid chromatography/tandem mass spectrometry; respectively. We used multivariable-adjusted linear regression models to relate each dietary pattern index (independent variables) to each proteomic and metabolomic marker (dependent variables). Of the 1373 proteins; 103 were associated with at least one dietary pattern (48 with AHEI; 83 with DASH; and 8 with MDS; all false discovery rate [FDR] ≤ 0.05). We identified unique associations between dietary patterns and proteins (17 with AHEI; 52 with DASH; and 3 with MDS; all FDR ≤ 0.05). Significant proteins enriched biological pathways involved in cellular metabolism/proliferation and immune response/inflammation. Of the 216 metabolites; 65 were associated with at least one dietary pattern (38 with AHEI; 43 with DASH; and 50 with MDS; all FDR ≤ 0.05). All three dietary patterns were associated with a common signature of 24 metabolites (63% lipids). Proteins and metabolites associated with dietary patterns may help characterize intermediate phenotypes that provide insights into the molecular mechanisms mediating diet-related disease. Our findings warrant replication in independent populations

Highlights

  • IntroductionData from clinical trials and prospective cohort studies indicate that healthy dietary patterns are associated with better metabolic health, lower risk of major chronic diseases, and lower mortality [2,3,4,5]

  • Sub-optimal diet quality is a leading cause of death in the United States and is estimated to contribute to approximately 44% of coronary heart disease deaths and 51% of stroke related deaths [1].Data from clinical trials and prospective cohort studies indicate that healthy dietary patterns are associated with better metabolic health, lower risk of major chronic diseases, and lower mortality [2,3,4,5].These studies indicate that diet quality may be a key factor in the prevention and mitigation of chronic disease

  • We present p/mQTL that were previously identified in the Framingham Offspring Study to be associated with proteins and/or metabolites that we observed to be significantly associated with at least one of the respective dietary patterns

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Summary

Introduction

Data from clinical trials and prospective cohort studies indicate that healthy dietary patterns are associated with better metabolic health, lower risk of major chronic diseases, and lower mortality [2,3,4,5]. These studies indicate that diet quality may be a key factor in the prevention and mitigation of chronic disease. Molecular biomarkers related to dietary intake may relate to risk factors for chronic disease, or overt chronic disease per se. Fewer studies have sought to relate dietary metabolomic profiles to disease outcomes; some studies have suggested that certain circulating metabolites may contribute to the biological underpinnings of diet–disease relations [7,8,9]

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