Metabolites, genomics, epigenomics, exposomics and health: Focus on serum bilirubin concentrations in subjects with metabolic syndrome from a Mediterranean population

Abstract

Although metabolomics aims at the measurement of small molecules (metabolites) in a biological sample, this knowledge requires additional information on the related genetic variants, epigenetic regulators and environmental factors (diet, smoking, physical activity, etc.) in order to translate the knowledge into actionable therapeutic or preventive evidence for complex disease outcomes. We focused on serum bilirubin, a metabolite generated when heme oxygenase catalyzes the degradation of heme (Figure 1). This produces biliverdin, which is converted into bilirubin by biliverdinreductase. Bilirubin is further processed in hepatocytes, where unconjugated bilirubin is conjugated by uridine diphosphate-glucuronosyltransferase (UDP-GT) to a water-soluble form for excretion. For decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice. However, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases.