Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis.

Adele Romano,Piero Del Boccio,Serena Longo,Anna M Giudetti,Marzia Friuli,Laura Del Coco,Silvia Valentinuzzi,Silvana Gaetani,Daniele Vergara,Ilaria Cicalini,Francesco P Fanizzi

doi:10.3390/nu13020394

Adele Romano, Piero Del Boccio + Show 9 more

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https://doi.org/10.3390/nu13020394

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Abstract

Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by 1H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg−1 i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.

Highlights

We found that the antilipogenic effect of OEA was associated with a decreased activity and expression of the key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), diacylglycerol acyltransferase (DGAT), and stearoyl-CoA desaturase 1 (SCD1)
An overall study of the lipid composition of hepatic homogenate from VEH and OEA rats was performed by 1NMR. 2D COSY, HSQC, HMBC and J-resolved spectra were randomly performed on samples and used to accurately assign the lipid classes present in samples
We demonstrated that chronic OEA treatment was able to affect hepatic sphingolipid metabolism, and to significantly decrease TAG level with concurrent reduction of PPARγ and sterol regulatory element-binding protein-1 (SREBP-1) protein expression

Summary

Introduction

The majority of OEA’s biological functions explains its potential interest as a pharmacological target for the treatment of obesity and eating-related disorders [1,15,16]. As a drug, OEA reduces food intake and body weight gain [3,17,18] in both lean and obese rodents. These effects are primarily related to the activation of the peroxisome proliferator-activated receptor-α (PPAR-α) [3,4,5,6,7], for which OEA shows high affinity

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