Large-scale metabolomic profiling and incident non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease with no specific drug therapy. High-throughput metabolomics present an unprecedented opportunity to identify biomarkers and potentially causal risk factors for NAFLD. Here, we determined the impact of 21 circulating metabolites, 17 lipids, and 132 lipoprotein particle characteristics on NAFLD combining prospective observational and two-sample Mendelian randomization (MR) analyses in 121,032 UK Biobank participants. We identified several metabolic factors associated with NAFLD risk in observational and MR analyses including triglyceride-rich and high-density lipoprotein particles composition, as well as the ratio of polyunsaturated fatty acids to total fatty acids. This study, is one of the largest to investigate incident NAFLD, provides concordant observational and genetic evidence that therapies aimed at reducing circulating triglycerides and increasing large HDL particles, as well as interventions aimed at increasing polyunsaturated fatty acid content may warrant further investigation into NAFLD prevention and treatment.

Automated summary

Non-alcoholic fatty liver disease (NAFLD) is a common disease without specific drug therapy. A study combining observational and Mendelian randomization analyses found that certain metabolic factors, such as triglyceride-rich and high-density lipoprotein particles composition, and the ratio of polyunsaturated fatty acids to total fatty acids, are associated with NAFLD risk. These findings provide evidence for potential therapeutic targets and interventions for NAFLD prevention and treatment.