Metabolomic Salivary Signature of Pediatric Obesity Related Liver Disease and Metabolic Syndrome

Abstract

Pediatric obesity-related metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are increasingly frequent conditions with a still-elusive diagnosis and low-efficacy treatment and monitoring options. In this study, we investigated the salivary metabolomic signature, which has been uncharacterized to date. In this pilot-nested case-control study over a transversal design, 41 subjects (23 obese patients and 18 normal weight (NW) healthy controls), characterized based on medical history, clinical, anthropometric, and laboratory data, were recruited. Liver involvement, defined according to ultrasonographic liver brightness, allowed for the allocation of the patients into four groups: obese with hepatic steatosis ([St+], n = 15) and without hepatic steatosis ([St–], n = 8), and with (n = 10) and without (n = 13) MetS. A partial least squares discriminant analysis (PLS-DA) model was devised to classify the patients’ classes based on their salivary metabolomic signature. Pediatric obesity and its related liver disease and metabolic syndrome appear to have distinct salivary metabolomic signatures. The difference is notable in metabolites involved in energy, amino and organic acid metabolism, as well as in intestinal bacteria metabolism, possibly reflecting diet, fatty acid synthase pathways, and the strict interaction between microbiota and intestinal mucins. This information expands the current understanding of NAFLD pathogenesis, potentially translating into better targeted monitoring and/or treatment strategies in the future.

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

“…Obese adolescents with and without NAFL and with and without metabolic syndrome (MetS) have been studied for their salivary metabolomic changes. Several fatty acids and sugars were reported to differ between these groups (Table 4) [215]. How NAFLD was diagnosed in adolescents, whether by ultrasound or liver enzyme elevations, made a significant difference to the metabolomic findings, especially with lipid profiles, and amino acid and ketone body plasma concentrations [216].…”

Exploring extra dimensions to capture saliva metabolite fingerprints from metabolically healthy and unhealthy obese patients by comprehensive two-dimensional gas chromatography featuring Tandem Ionization mass spectrometry

“…Urea, another informative analyte from the fingerprinting analysis, is the principal carrier of waste nitrogen derived from the protein catabolism. High levels of salivary urea were found to be abundant in chronic kidney disease patients [ 50 ], while higher D-(+)-glucuronic acid γ-lactone amounts were found in patients with hepatic steatosis [ 51 ]. On the other hand, 5-aminovaleric acid (+75.3% in MUO), a lysine degradation product, is a normal metabolite present in human saliva, with a tendency to elevated concentration in patients with chronic periodontitis.…”

The Liver in Children With Metabolic Syndrome

“…Further studies have recently confirmed as different salivary metabolic profiles characterized pediatric obesity, liver disease, and MetS (212, 213). Troisi et al (213) observed high levels of two saturated fatty acids, palmitic, and myristic acid, in children with steatosis. Wasilewska et al (214) demonstrated a positive correlation between total ceramide concentration and IR markers in obese children with NAFLD.…”