Ricerc@Sapienza

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common multi-factorial disease characterized by increased hepatic fat. Although NAFLD associates with the risk of atherosclerotic cardiovascular disease (ASCVD), this risk could differ in the different NAFLD subtypes, e.g. metabolically or genetically driven.
The I148M PNPLA3 variant accounts for the largest fraction of genetic predisposition to NAFLD independent from metabolic risk factors. Recently, comparing subjects with Metabolic NAFLD due to metabolic disturbances to those with Genetic NAFLD due to PNPLA3 MM genotype, we found that excess hepatic fat (HF) increases the burden of subclinical atherosclerosis, as estimated by carotid intima-media thickness, only in Metabolic NAFLD.
It is well known that postprandial lipemia is an important cardiometabolic risk factor superior to fasting lipid levels in predicting atherosclerosis risk. Several lines of evidences have shown a close correlation between liver fat content and postprandial lipid disturbances. Moreover, NAFLD patients developing ASCVD have increased concentration of remnants, a lipoprotein class mainly generated during the post-prandial period. Therefore, we have hypothesized that the increased risk of vascular damage associated to Metabolic NAFLD may be related to a delay in the lipid and lipoprotein metabolism during the post-prandial phase as compared to Genetic NAFLD.
Few studies have investigated the postprandial metabolism of lipoproteins in NAFLD and none have separately considered metabolically vs. genetically driven NAFLD. Thus, we aim to investigate if there are any differences in the dynamic response of lipoprotein metabolism after an oral high fat meal in: 1) 15 subjects with, PNPLA3 wild-type genotype, MRS-defined NAFLD and metabolic syndrome (Metabolic group), 2) 10 blood donors carrying M148M PNPLA3 genotype with MRS-defined NAFLD (Genetic group) and 3) 20 blood donors, PNPLA3 wild-types and without MRS-defined NAFLD (Controls).