The effect of Oleoylethanolamide supplementation on PPAR-α gene expression, some inflammatory biomarkers and the abundance of Akkermansia muciniphila bacteria in the stool samples of obese people: A double-blind randomized placebo-controlled clinical trial

Abstract

Background: Obesity is a serious public health problem worldwide and involves in the pathophysiology of many chronic diseases. One of the well-established regulatory systems in the energy homeostasis and appetite control is the endocannabinoid system. Endocannabinoid-like compounds such as oleoylethanolamide are the bioactive lipid components with similar biosynthetic and degradation pathways to the endocannabinoid system; however, they are unable to bind to the cannabinoid receptors. An imbalance in the gut microbiota population, low-grade inflammation, and dysregulation of endocannabinoid system tone involve in the pathogenesis of obesity. The present study was aimed to investigate the effects of Oleoylethanolamide supplementation on proximal proliferatoractivated receptor-α (PPAR-α) gene expression, some inflammatory biomarkers and the abundance of Akkermansia muciniphila bacteria in the stools of obese people. Methods and Materials: This randomized, double-blind, placebo-controlled clinical trial was carried out on 60 healthy obese adult people in Tabriz, Iran, in 2016. The eligible subjects were divided into an intervention group (who received two 125 mg OEA capsules daily) and a placebo group (who received the same amount of starches) and treated for 8 weeks. A written consent form was completed at baseline by participants. At baseline and at the end of the study, blood and stool samples were collected in fasting state. As well as, visual analog scales (VAS) questionnaire and anthropometric measurements were assessed before and after study. The levels of IL-6, TNF-α and hs-CRP were assessed by ELISA and Immunoturbidimetry methods respectively. The abundance of Akkermansia muciniphila bacteria in the stool samples and the expression of PPAR-α gene in the blood samples were evaluated by real-time PCR technique. Results: Of 60 obese people recruited to the study, finally 56 (n=27 in the intervention, n=29 in the placebo group) participants completed the intervention. Mean ± SD ages of participants in the intervention and placebo groups were 37.37 ± 8.74 and 38.13 ± 9.28 years, respectively. About 55% and 65% of participants in the intervention and placebo groups, respectively, were females. PPAR-α gene expression in the intervention group was increased significantly in comparison to the placebo group (p<0.001). The abundance of Akkermansiamuciniphila bacteria was increased slightly but significantly in the intervention group (p<0.001). Weight, body mass index (BMI), waist circumference (WC) and WC/hip circumference ratio were decreased significantly in the intervention (p<0.001). According to the results of the appetite questionnaire, hunger, desire to eat and cravings to eat sweet foods decreased significantly (p<0.05), and fullness increased significantly (p<0.01). Changes in other items were not significant. The serum levels of IL-6 and TNF-α decreased significantly (p=0.001, p<0.001), however, a significant change was not observed in the hs-CRP variable (p>0.05). Conclusion: The results of the present study revealed a positive effect on the factors related to the energy homeostasis, appetite and inflammatory biomarkers that are involved in the management of obesity. However, future studies with longer duration are suggested to confirm obtained results.