Department of Pharmacology and Pharmacotheraphy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
FASEB J. 2011 Feb;25(2):765-74. doi: 10.1096/fj.10-166595. Epub 2010 Oct 19.
This study was undertaken to investigate the link between dietary fat content and intestinal levels of anorectic N-acylethanolamines (NAEs), including oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA). Male rats were fed high-fat diets (HFDs) with variable percentages of fat [20-45% of total energy (E%)] for 1-7 d; afterward, the jejunums were isolated, and jejunal NAE levels were measured by liquid-chromatography mass spectrometry. Enzyme activities and mRNA expression levels were measured for two synthesizing enzymes, N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and glycerophosphodiesterase (GDE1), and one degrading enzyme, fatty acid amide hydrolase (FAAH). We found a dose-response relation between the quantity/percentage of dietary fat, irrespective of the energy density, and the reduction of intestinal levels of OEA, PEA, and LEA. The reductions were present after 1 d of 45E% HFD. LEA, the major NAE species, was shown to have an anorectic potency slightly less than that of OEA but higher than PEA. Regulation at the enzyme level seems not to explain the changes in NAE levels. The results suggest the presence of a fat sensor, mediating the reduced intestinal NAE levels. The intestinal NAE levels are reduced in a dose- and time-dependent manner in response to dietary fat intake, and this may contribute to the well-known hyperphagic effect of HFDs.
本研究旨在探讨膳食脂肪含量与肠道厌食性 N-酰基乙醇胺（NAE）水平之间的联系，包括油酰乙醇胺（OEA）、棕榈酰乙醇胺（PEA）和亚油酸乙醇胺（LEA）。雄性大鼠用不同脂肪含量的高脂肪饮食（HFD）喂养[总能量（E%）的 20-45%]1-7 天；之后，分离空肠，并通过液相色谱-质谱法测量空肠 NAE 水平。测量两种合成酶（N-酰基磷脂酰乙醇胺特异性磷脂酶 D（NAPE-PLD）和甘油磷酸二酯酶（GDE1）和一种降解酶（脂肪酸酰胺水解酶（FAAH）的酶活性和 mRNA 表达水平。我们发现，无论能量密度如何，膳食脂肪的数量/百分比与肠道 OEA、PEA 和 LEA 水平的降低之间存在剂量反应关系。45E%HFD 喂养 1 天后就出现了这种降低。LEA 是主要的 NAE 种类，其厌食效力略低于 OEA，但高于 PEA。在酶水平的调节似乎不能解释 NAE 水平的变化。结果表明存在一种脂肪传感器，介导肠道 NAE 水平的降低。肠道 NAE 水平以剂量和时间依赖的方式对膳食脂肪摄入作出反应而降低，这可能有助于解释 HFD 众所周知的促食作用。
