The Type 2 Diabetes Susceptibility PROX1 Gene Variants Are Associated With Postprandial Plasma Metabolites Profile in Non-Diabetic Men

Nutrients. 2019 Apr 19;11(4):882. doi: 10.3390/nu11040882.

Abstract

The prospero homeobox 1 (PROX1) gene may show pleiotropic effects on metabolism. We evaluated postprandial metabolic alterations dependently on the rs340874 genotypes, and 28 non-diabetic men were divided into two groups: high-risk (HR)-genotype (CC-genotype carriers, n = 12, 35.3 ± 9.5 years old) and low-risk (LR)-genotype (allele T carriers, n = 16, 36.3 ± 7.0 years old). Subjects participated in two meal-challenge-tests with high-carbohydrate (HC, carbohydrates 89%) and normo-carbohydrate (NC, carbohydrates 45%) meal intake. Fasting and 30, 60, 120, and 180 min after meal intake plasma samples were fingerprinted by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). In HR-genotype men, the area under the curve (AUC) of acetylcarnitine levels was higher after the HC-meal [+92%, variable importance in the projection (VIP) = 2.88] and the NC-meal (+55%, VIP = 2.00) intake. After the NC-meal, the HR-risk genotype carriers presented lower AUCs of oxidized fatty acids (-81-66%, VIP = 1.43-3.16) and higher linoleic acid (+80%, VIP = 2.29), while after the HC-meal, they presented lower AUCs of ornithine (-45%, VIP = 1.83), sphingosine (-48%, VIP = 2.78), linoleamide (-45%, VIP = 1.51), and several lysophospholipids (-40-56%, VIP = 1.72-2.16). Moreover, lower AUC (-59%, VIP = 2.43) of taurocholate after the HC-meal and higher (+70%, VIP = 1.42) glycodeoxycholate levels after the NC-meal were observed. Our results revealed differences in postprandial metabolites from inflammatory and oxidative stress pathways, bile acids signaling, and lipid metabolism in PROX1 HR-genotype men. Further investigations of diet-genes interactions by which PROX1 may promote T2DM development are needed.

Keywords: PROX1 gene; high-carbohydrate meal; normo-carbohydrate meal; nutrigenetics; nutrimetabolomics; postprandial metabolic fingerprinting; type 2 diabetes mellitus risk; ultra-high performance liquid chromatography.

MeSH terms

  • Acetylcarnitine / blood
  • Adult
  • Alleles
  • Bile Acids and Salts / blood*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diet
  • Dietary Carbohydrates / metabolism*
  • Gene-Environment Interaction
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Inflammation / blood*
  • Linoleic Acids / blood
  • Lipid Metabolism / genetics*
  • Male
  • Meals
  • Metabolome
  • Ornithine / blood
  • Oxidative Stress
  • Polymorphism, Single Nucleotide*
  • Postprandial Period
  • Signal Transduction
  • Sphingosine / blood
  • Tumor Suppressor Proteins / genetics*

Substances

  • Bile Acids and Salts
  • Dietary Carbohydrates
  • Homeodomain Proteins
  • Linoleic Acids
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein
  • linoleamide
  • Acetylcarnitine
  • Ornithine
  • Sphingosine