Effects of oleoylethanolamide supplementation on atherogenic indices and hematological parameters in patients with nonalcoholic fatty liver disease: A clinical trial

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in the world. The current interventional trial aimed to evaluate the effects of supplementation with oleoylethanolamide (OEA) in combination with weight loss intervention on some atherogenic indices as well as hematological parameters in patients newly diagnosed with NAFLD. Methods: In this triple-blinded, randomized, placebo-controlled clinical trial, 76 obese patients with NAFLD confirmed by ultra-sonographic findings were randomly assigned to receive a weight reduction diet plus either 250 mg OEA (n=38) or placebo (n=38) for 12 weeks. Atherogenic factors including total cholesterol/high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)/HDL-C, triglyceride (TG)/HDL-C, non-HDL-C/HDL-C ratios and non-HDL-C level, as well as hematological parameters were assessed before and after intervention. Results: After adjustment for potential confounding factors, between group analyses demonstrated a significantly lower LDL-C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios in the OEA group compared to the placebo, post-intervention (95% confidence interval [CI]:0.06 to 0.85, P = 0.024; 95% CI: -2.06 to -0.05, P = 0.039; 95% CI: -1.05 to -0.02, P = 0.042,respectively). Additionally, OEA supplementation could significantly decrease the levels of red blood cell distribution width (RDW) compared to the placebo at the endpoint after considering potential confounding variables (95% CI: -0.56 to -0.003, P = 0.041). No significant differences were found between the two study groups in terms of other hematological parameters. Conclusion: The results of the current study indicated that OEA supplementation had beneficial effects on LDL-C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios as well as RDW in obese patients with NAFLD. Trial Registration: IRCT20110530006652N2; https://www.irct.ir/trial/37228.

T329S Mutation in the FMO3 Gene Alleviates Lipid Metabolic Diseases in Chickens in the Late Laying Period

“…Compared with the conventional lipid parameters, the non-HDL-C, TC/HDL-C, AIS, and LCI ratios are better indicators of AS, a disease that is positively associated with FLD [ 46 ]. These ratios have been suggested to be accurate predictors of AS [ 47 ].…”

Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats

“…In fact, as a drug, OEA reduces food intake and body weight gain [20,27,28] in both lean and obese rodents and reduces lipopolysaccharide-induced liver injury in mice [29]. Moreover, it has been demonstrated that OEA reduces lipid synthesis and lipoprotein secretion in hepatocytes [30] and improves HFD-induced liver steatosis in rats [31] and humans [32,33]. Recently, we demonstrated that OEA decreases hepatic lipid accumulation through a peroxisome proliferator-activated receptor γ (PPARγ)-mediated inhibition of hepatic fatty acid uptake and triacylglycerol synthesis [34].…”

In vivo brain levels of acetylcholine and 5‐hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

“…Activation of PPAR is related to the modulation of multiple physiological processes, including cell metabolism, cancer, cardiovascular functioning, and so forth (Jumpertz et al, 2011; Tan et al, 2021; Wagner & Wagner, 2020b). Among the endogenous ligands that activate PPARα are the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA; Carta et al, 2015; Chen et al, 2015; Grygiel‐Górniak, 2014; Tutunchi et al, 2019; Tutunchi, Naeini, Saghafi‐Asl, Farrin, et al, 2020; Tutunchi, Ostadrahimi, Saghafi‐Asl, Hosseinzadeh‐Attar, et al, 2020; Tutunchi, Saghafi‐Asl, & Ostadrahimi, 2020). The biological relevance of PPARα has been focus of study since this receptor has been mapped in the central nervous system (Nisbett & Pinna, 2018; Warden et al, 2016; Wójtowicz et al, 2020), leading to the hypothesis that cerebral functions might be under the influence of PPARα (Nisbett & Pinna, 2018; Warden et al, 2016; Wójtowicz et al, 2020).…”

“…Several natural or synthetic agonists of PPARs have been used to study the mechanism of action of these receptors (Nabavi et al, 2020; Puligheddu et al, 2013; Wagner & Wagner, 2020b). In this regard, PPARα is activated by endogenous ligands, including the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), triggering mechanisms involved in the modulation of multiple biological functions (Carta et al, 2015; Chen et al, 2015; Fidaleo et al, 2014; Fu et al, 2005; Grygiel‐Górniak, 2014; Rodríguez de Fonseca et al, 2001; Tutunchi et al, 2019; Tutunchi, Naeini, Saghafi‐Asl, Farrin, et al, 2020; Tutunchi, Ostadrahimi, Saghafi‐Asl, Hosseinzadeh‐Attar, et al, 2020; Tutunchi, Ostadrahimi, Saghafi‐Asl, Roshanravan, et al, 2020; Tutunchi, Saghafi‐Asl, & Ostadrahimi, 2020). At present, special attention is focused on the localization of PPARα in several tissues suggesting an active role of this receptor on the control of physiological functions.…”