Background

Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version) are limited.

Objectives

The goal was to determine a pattern of metabolites associated with the Healthy Eating Index (HEI)-2015, which measures adherence to the Dietary Guidelines for Americans.

Methods

The analysis examined 3557 adult men and women from the longitudinal cohort Multiethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens and diet and demographic questionnaires were assessed at baseline. Untargeted ¹H 1-dimensional nuclei magnetic resonance spectroscopy (600 MHz) was used to generate metabolomics and lipidomics. A metabolome-wide association study specified each spectral feature as outcomes, HEI-2015 score as predictor, adjusting for age, sex, race, and study site in linear regression analyses. Subsequently, hierarchical clustering defined the discrete groups of correlated nuclei magnetic resonance features associated with named metabolites, and the linear regression analysis assessed for associations with HEI-2015 total and component scores.

Results

The sample included 50% women with an mean age of 63 years, with 40% identifying as White, 23% as Black, 24% as Hispanic, and 13% as Chinese American. The mean HEI-2015 score was 66. The metabolome-wide association study identified 179 spectral features significantly associated with HEI-2015 score. The cluster analysis identified 7 clusters representing 4 metabolites; HEI-2015 score was significantly associated with all. HEI-2015 score was associated with proline betaine [β = 0.12 (SE = 0.02); P = 4.70 × 10^-13] and was inversely related to proline [β = -0.13 (SE = 0.02); P = 4.45 × 10^-14], 1,5 anhydrosorbitol [β = -0.08 (SE = 0.02); P = 4.37 × 10^-7] and unsaturated fatty acyl chains [β = 0.08 (SE = 0.02); P = 8.98 × 10^-7]. Intake of total fruit, whole grains, and seafood and plant proteins was associated with proline betaine.

Conclusions

Diet quality is significantly associated with unsaturated fatty acyl chains, proline betaine, and proline. Further analysis may clarify the link between diet quality, metabolites, and pathogenesis of cardiometabolic disease.

Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted ¹H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted ¹H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P=4.88×10^-20-1.16×10^-3). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P=1.90×10^-35-8.46×10^-7), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d^-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.