Diep Thi Ai, Madsen Andreas N, Krogh-Hansen Sandra, Al-Shahwani Marwa, Al-Sabagh Laila, Holst Birgitte, Hansen Harald S
Department of Drug Design & Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2014 Jun 24;9(6):e100365. doi: 10.1371/journal.pone.0100365. eCollection 2014.
Oleoylethanolamide and several other N-acylethanolamines (NAEs), e.g. linoleoylethanolamide and palmitoylethanolamide, have anorectic properties in rats, and prolonged intake of a high-fat diet decreases the levels of the anorectic NAEs in jejunum. Jejunal anorectic NAEs are thought to add to the control of food intake via activation of PPARalpha and the vagus nerve. The fat-induced decrease may explain part of the hyperphagic effect of high-fat diets. In the present study, we investigated 1) whether the reduced levels of anorectic NAEs were reversible in rats, 2) whether mice respond to dietary fat (olive oil) by reducing levels of anorectic NAEs, and 3) whether dietary non-esterified oleic acid also can decrease levels of anorectic NAEs in mice. We are searching for the fat sensor in the intestine, which mediates the decreased levels of anorectic NAEs.
Male rats and mice were fed diets high (45 energy% fat) in either triacylglycerol or free fatty acids for 7-14 days, and jejunal NAE and N-acylphosphatidylethanolamine (NAPE) levels were determined by liquid-chromatography mass spectrometry.
In rats, reduced levels of anorectic NAEs could be reversed after 3 days from changing the diet from high-fat to chow. Corresponding NAPE levels tended to show the same changes. In mice, jejunal levels of anorectic NAEs were also reduced when fed a high-fat diet. In addition, we found that non-esterified oleic acid were also able to reduce levels of anorectic NAEs in mice.
These results suggest that the down-regulation of the jejunal level of anorectic NAEs by dietary fat is not restricted to rats, and that the fatty acid component oleic acid, in dietary olive oil may be sufficient to mediate this regulation. Thus, a fatty acid sensor may mediate this effect of dietary fat.
油酰乙醇胺和其他几种N-酰基乙醇胺（NAEs），如亚油酰乙醇胺和棕榈酰乙醇胺，在大鼠中具有厌食特性，长期摄入高脂饮食会降低空肠中厌食性NAEs的水平。空肠中的厌食性NAEs被认为通过激活过氧化物酶体增殖物激活受体α（PPARα）和迷走神经来参与食物摄入的控制。脂肪诱导的水平降低可能解释了高脂饮食的部分贪食效应。在本研究中，我们调查了：1）大鼠中厌食性NAEs水平的降低是否可逆；2）小鼠是否会通过降低厌食性NAEs水平来对膳食脂肪（橄榄油）作出反应；3）膳食中非酯化油酸是否也能降低小鼠中厌食性NAEs的水平。我们正在寻找肠道中的脂肪传感器，它介导了厌食性NAEs水平的降低。
雄性大鼠和小鼠分别喂食富含三酰甘油或游离脂肪酸的高脂饮食（45%能量来自脂肪）7 - 14天，通过液相色谱 - 质谱法测定空肠中NAE和N-酰基磷脂酰乙醇胺（NAPE）的水平。
在大鼠中，将饮食从高脂改为普通饲料3天后，厌食性NAEs降低的水平可以逆转。相应的NAPE水平也有相同的变化趋势。在小鼠中，喂食高脂饮食时空肠中厌食性NAEs的水平也会降低。此外，我们发现非酯化油酸也能够降低小鼠中厌食性NAEs的水平。
这些结果表明，膳食脂肪对空肠中厌食性NAEs水平的下调作用不仅限于大鼠，膳食橄榄油中的脂肪酸成分油酸可能足以介导这种调节。因此，一种脂肪酸传感器可能介导了膳食脂肪的这种作用。
