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.
Highlights
The incidence of obesity and its related conditions, including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD), has dramatically increased worldwide in all age groups including pediatrics [1]
We have recently shown a complex network of urinary molecules prevalently represented by intestinally-derived bacterial products [14] which are correlated with the clinical phenotype and can differentiate between normal weight and obese children, distinguishing between those with and without liver involvement, based on the characteristics of their gut-liver axis (GLA) function [15]
We showed that salivary testing of uric acid, glucose, insulin and HOMA together with selected anthropometric parameters may help to identify noninvasively obese children with hepatic steatosis and/or having MetS components [4]
Summary
The incidence of obesity and its related conditions, including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD), has dramatically increased worldwide in all age groups including pediatrics [1]. Pediatric obesity definitely is an early risk factor for adult morbidity and Nutrients 2019, 11, 274; doi:10.3390/nu11020274 www.mdpi.com/journal/nutrients. Due to the existence of a well-established tracking phenomenon, the early detection and treatment of MetS and fatty liver in childhood represents a valuable tool to prevent further health complications and to minimize the global socioeconomic burden of hepato-metabolic and cardiovascular obesity-associated complications in adulthood [4]. Metabolomics has recently started to pave the way to a better pathomechanistic understanding of these hepatometabolic complications, leading to a more efficient diagnosis and better therapeutic approaches In this regard, studies have shown that high urinary/blood levels of aromatic (AAA) ±
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