Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
Nutrients. 2021 Jan 27;13(2):394. doi: 10.3390/nu13020394.
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 H-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 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.
油酰乙醇胺（OEA）是一种天然存在的生物活性脂质，属于 N-酰基乙醇酰胺家族。OEA 具有多种有益作用，尽管人们更感兴趣的是它在治疗肥胖、脂肪肝和与饮食有关的疾病方面的潜在作用。为了更好地阐明 OEA 在肝脏中的抗脂肪生成作用机制，我们通过 H-NMR、LC-MS/MS 和薄层色谱分析进行了脂质组学研究，评估了大鼠肝脏的全脂质组成，在两周内每天用 OEA（10 mg/kg，腹腔注射）处理。我们发现 OEA 可显著降低肝三酰基甘油（TAG）含量，并显著改变鞘脂组成和神经酰胺酶活性。我们将 OEA 的抗脂肪生成作用与参与脂肪酸和 TAG 合成的关键酶的活性和表达降低相关联，如乙酰辅酶 A 羧化酶、脂肪酸合成酶、二酰基甘油酰基转移酶和硬脂酰辅酶 A 去饱和酶 1。此外，我们发现 OEA 处理大鼠肝脏中的 SREBP-1 和 PPARγ 蛋白表达均显著降低。我们的研究结果为 OEA 对肝脂肪生成的分子机制提供了重要的新见解，并提示 OEA 诱导的鞘脂代谢变化与抑制肝 TAG 水平之间可能存在联系。
