The lipidome in nonalcoholic fatty liver disease: actionable targets

PIROLA, CARLOS J.; SOOKOIAN, SILVIA

JLR PAPERS IN PRESS

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2021 vol. 62 p. 1 - 15

0022-2275

Nonalcoholic fatty liver disease (NAFLD)has become the most prevalent chronic liver disease.Recent technological advances, combined with OMICsexperiments and explorations involving differentbiological samples, have uncovered vital aspects ofNAFLD biology. In this review, we summarize recentwork by our group and others that expands what isknown about the role of lipidome in NAFLD patho-genesis. We discuss how pathway and enrichment an-alyses were performed by integrating a list of querymetabolites derived from text-mining existingNAFLD-lipidomics studies, resulting in the identifi-cation of nine Kyoto Encyclopedia of Genes and Ge-nomes dysregulated pathways, including biosynthesisof unsaturated fatty acids, butanoate metabolism,synthesis and degradation of ketone bodies, sphingo-lipid, arachidonic acid and pyruvate metabolism, andnumerous nonsteroidal antiinflammatory drug path-ways predicted from The Small Molecule PathwayDatabase. We also summarize an integrated pathway-level analysis of genes and lipid-related metabolitesassociated with NAFLD, which shows over-representation of signal transduction, seleniummicronutrient network, Class A/1Rhodopsin-like re-ceptors and G protein-coupled receptor ligand bind-ing, and G protein-coupled receptor downstreamsignaling. Generated gene-metabolite-disease interac-tion networks indicate that NAFLD and arterial hy-pertension are interlinked by molecular signatures.Finally, we discuss how mining pathways and associa-tions among metabolites, lipids, genes, and proteinscan be exploited to infer networks and potentialpharmacological targets and how lipidomic studiesmay provide insight into the interrelationships amongmetabolite clusters that modify NAFLD biology, ge-netic susceptibility, diet, and the gut microbiome.