To describe the recent advances in our understanding of fatty acids and lipids in paediatric nonalcoholic fatty liver disease (NAFLD) and their future implications.
Data have been accumulated to suggest that ceramides are the main drivers of hepatic insulin resistance in NAFLD, and inhibition of ceramide synthesis improves histology in mice.
Saturated fatty acids formed by de novo lipogenesis generate increased lipotoxicity compared with dietary-derived saturated fatty acids.
Hepatic lipogenesis and associated insulin resistance have been found to be influenced by several novel proteins, including E2F1, cyclic AMP response element binding protein transcriptional coactivator 2, Raptor, and eukaryotic initiation factor 6. There are encouraging data from animal models that modulation of these could be therapeutic targets.
Human and animal metabolomics and lipidomics data have been used to generate a lipid signature for NAFLD and nonalcoholic steatohepatitis. Serum lipidomics appears to correlate with hepatic lipidomics.
Therapeutic trials of polyunsaturated fatty acids in children have had mixed results, with some reductions in noninvasive biomarkers.
Multiple new pathways for drug targets have been identified, and use of lipidomics is likely to become a noninvasive method for assessing disease. However, much of the data for paediatric NAFLD are extrapolated from adult or animal studies.
aDepartment of Paediatrics, University of Cambridge, Cambridge, UK
bDepartment of Pediatric Gastroenterology, University of California San Diego (UCSD)
cRady Children's Hospital, San Diego, California, USA
eLiver Research Unit, Bambino Gesu Hospital, IRCCS, Rome, Italy
Correspondence to Dr Valerio Nobili, Department of Hepatogastroenterology & Nutrition, Pediatric Hospital IRCCS ‘Bambino Gesù’, Via S. Onofrio 4, 00165 Rome, Italy. Tel: +39 06 68 59 22 43; fax: +39 06 68 59 21 920; e-mail: firstname.lastname@example.org