Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics

As a result of the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) represents a global medical concern in childhood with a closely related increased cardiometabolic risk. Knowledge on NAFLD pathophysiology has been largely expanded over the last decades. Besides the well-known key NAFLD genes (including the I148M variant of the PNPLA3 gene, the E167K allele of the TM6SF2, the GCKR gene, the MBOAT7-TMC4 rs641738 variant, and the rs72613567:TA variant in the HSD17B13 gene), an intriguing pathogenic role has also been demonstrated for the gut microbiota. More interestingly, evidence has added new factors involved in the "multiple hits" theory. In particular, omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment. In fact, different branches of omics including metabolomics, lipidomics (in particular sphingolipids and ceramides), transcriptomics (including micro RNAs), epigenomics (such as DNA methylation), proteomics, and glycomics represent the most attractive pathogenic elements in NAFLD development, by providing insightful perspectives in this field. In this perspective, we aimed to provide a comprehensive overview of NAFLD pathophysiology in children, from the oldest pathogenic elements (including genetics) to the newest intriguing perspectives (such as omics branches).