Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial

Background: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1a, PPAR-g, CEBP-a and CEBP-b genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD).Methods: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. Results: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1a (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-g, CEBP-a and CEBP-b between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1a as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in tri-glyceride was inversely correlated with percent of changes in the expression levels of SIRT1.Conclusion: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "Registered under Iranian Registry of Clinical Trials Identifier no: IRCT20090609002017N32".(c) 2023 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.