Effects of oleoylethanolamide supplementation on the expression of PPAR-α, UCP1 and UCP2 genes, metabolic parameters, and anthropometric indices among obese adult with non-alcoholic fatty liver disease: A triple-blind randomized controlled clinical trial

Abstract

Background: Due to the high prevalence of non-alcoholic fatty liver disease (NAFLD), effective treatment strategies are of primary importance for the prevention and treatment of NAFLD. The objective of the present study was to examine the effects of OEA supplementation on the expression of PPAR-α, uncoupling proteins 1and 2 (UCP1 and UCP2) genes in the peripheral blood mononuclear cells (PBMCs), metabolic parameters, and anthropometric indices among obese patients with NAFLD.

Methods: This triple-blind placebo-controlled randomized clinical trial was conducted on 76 obese patients with NAFLD. Eligible individuals were randomly divided into intervention and placebo groups (n=38 in each group). The intervention group received two 125-mg OEA capsules daily and the placebo group received similar doses of starch capsules for 12 weeks. Anthropometric measurments, diet, appetite sensation, physical activity level as well as lipid profile, glycemic parameters, serum liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkalin phosphatase (ALP), and ALT/AST ratio were assessed at baseline and at the end of the study. The mRNA expression levels of PPAR-α, UCP1, and UCP2 were assessed using real-time polymerase chain reaction (RT-PCR) technique at pre-and post-intervention phase. To contorl confounding factors, three separate models which included baseline values (model 1), baseline values, age, changes in physical activity and energy intake (model 2), and baseline values, age, changes in physical activity, energy intake, and BMI (model 3) were applied.

Results: A significant decrease (P<0.05) in the anthropometric indices, energy and carbohydrate intakes were observed in the OEA group, compared to the placebo group at the end of the study. However, there were no significant differences in fat and protein intakes between the two groups at the end-point. Hunger, feeling to eat, and desire to eat sweet foods decreased significantly and feeling of fullness increased significantly in the OEA group, compared to the placebo at the end of the trial, after adjusting for the parameters with confounding effects based on the two models. However, no significant differences were observed in these parameters between the two groups after adjusting for the potential confounders based on Model 3. There was a significant increase (P<0.01) in the expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, compared to the placebo at the endpoint. After adjusting for the potential confounders based on Model 1 and Model 2, OEA treatment significantly (P<0.05) resulted in decreased serum levels of triglyceride (TG), ALT, AST, ALT/AST, and increased serum levels of high-density lipoprotein cholesterol (HDL-C). However, these parameters lost their significant levels after adjusting for the potential confounders based on Model 3. After adjusting for the potential confounders based on three proposed models, serum levels of fasting blood sugar (FBS), insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) significantly decreased (P<0.01) in the OEA group, compared to the placebo. There were no significant between-group differences in liver steatosis severity and NAFLD fibrosis score post-intervention.

Conclusion: In conclusion, the present study, for the first time, revealed that OEA supplementation significantly improved some of the risk factors associated with NAFLD including anthropometric indices, glycemic parameters, lipid profile, and serum ALT and AST levels. Future studies with larger sample sizes and longer duration are required to verify our results.