The effects of oleoylethanolamide, an endogenous PPAR‐α agonist, on risk factors for NAFLD: A systematic review

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease.Recently, some novel compounds have been investigated for the prevention and treatment of NAFLD. Oleoylethanolamide (OEA), an endogenous PPAR-α agonist, has exhibited a plethora of pharmacological properties for the treatment of obesity and other obesity-associated metabolic complications. This systematic review was performed with a focus on the effects of OEA on the risk factors for NAFLD.PubMed, Scopus, Embase, ProQuest, and Google Scholar databases were searched up to December 2018 using relevant keywords. All articles written in English evaluating the effects of OEA on the risk factors for NAFLD were eligible for the review. The evidence reviewed in this article illustrates that OEA regulates multiple biological processes associated with NAFLD, including lipid metabolism, inflammation, oxidative stress, and energy homeostasis through different mechanisms. In summary, many beneficial effects of OEA have led to the understanding that OEA may be an effective therapeutic strategy for the management of NAFLD. Although a wide range of studies have demonstrated the most useful effects of OEA on NAFLD and the associated risk factors, further clinical trials, from both in vivo studies and in vitro experiments, are warranted to verify these outcomes.

Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19

“…OEA, a high affinity endogenous ligand of PPAR-α (28), binds to PPAR-α receptors, and increases the expression level of anti-inflammatory cytokine such as IL-10. In addition, it attenuates the inflammatory responses and decreases the expression of TLR4, and interfering with the ERK1/2/AP-1/STAT3 signaling cascade (29)(30)(31). In a recent clinical trial, OEA supplementation could decrease inflammation in obese patients via reducing serum concentrations of inflammatory markers including IL-6 and TNF-α (32).…”

A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity

“…Obese phenotype, glucose intolerance, higher levels of circulating cholesterol and triglycerides, inflammation of the adipose tissue, changes in the gut microbiota, an altered browning programme, and defective thermogenesis were observed in adipose tissue of NAPE‐PLD‐deleted mice . Oleoylethanolamide has been found in different tissues such as the gastrointestinal tract, muscle, adipocytes, liver, kidney, heart, lung, pancreas, brain, and salivary gland . The formation of OEA in the intestine is mainly stimulated by ingestion of a diet in which the OA is high .…”

“…Nevertheless, the high expression level of CB2R was found in the immune system, and to a lesser extent, in adipose tissue, muscle, liver, and intestine . Endocannabinoids play a crucial role in relieving pain symptoms and enhancing appetite, especially in those patients suffering from cachexia and malnutrition . Arachidonoylethanolamide and 2‐AG, as derivatives of arachidonic acid (AA), are considered to be the most important endocannabinoids, which increase the caloric intake and reduce EE, resulting in augmented energy consumption .…”

“…Indeed, endocannabinoid‐like compounds induce other gene receptors involved in metabolic processes. OEA, a derivative of OA, is considered as an endocannabinoid‐like compound . Oleoylethanolamide functions in a CBR‐independent manner, and causes hypophagia; thus, this bioactive lipid mediator may participate in the modulation of eating behaviour …”

“…The biochemical structure of OEA is presented in Figure . OEA is derived from oleic acid (OA), a monounsaturated fatty acid, which has beneficial effects on body composition and regional fat distribution . The role of OEA in the modulation of food intake and weight management makes it an attractive molecule requiring further exploration in obesogenic environments.…”