DESATURATION OF ESSENTIAL FATTY ACIDS USING STABLE ISOTOPE GC-MS

使用稳定同位素 GC-MS 使必需脂肪酸去饱和

• 批准号: 3789529
• 负责人: N SALEM
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3789529
• 关键词: Macaca mulatta; alcoholism /alcohol abuse; analytical chemistry; arachidonate; brain metabolism; cats; dietary lipid; drug withdrawal; essential fatty acids; ethanol; fatty acid metabolism; gas chromatography mass spectrometry; laboratory mouse; laboratory rat; linoleate; linolenate; nutrient drug interaction; nutrition related tag; omega 3 fatty acid; stable isotope; unsaturated fatty acids

Desaturation and elongation are necessary steps in the modification of the essential fatty acids EFA), linoleic (18:2n6) and linolenic (18:3n3) acids, to arachidonic (20:4n6) and docosahexaenoic (22:6n3) acids, respectively. The levels of the latter two fatty acids are lowered by ethanol consumption in blood cells, liver and brain in animals. We have shown that the mechanisms underlying the disruption of essential fatty acid levels in these tissues are in part due to the inhibition of the elongation/desaturation of 18-carbon essential fatty acids by alcohol. A stable isotope gas chromatography-mass spectrometry (GC-MS) method has been developed that allows for the in vivo examination of these processes. This method has improved the sensitivity of studies in large animals. Studies in mice, rats, cats and rhesus monkeys have suggested that all mammals have elongation and desaturation capability and that heir products may be monitored in the blood supply. Felines, which had been given alcohol for 14 weeks, showed an 80% reduction in 20:4n6 and eicosapentaenoic (20:5n3) acid in the liver and blood together with a decrease in the metabolism of deuterated 18:2n6 and 18:3n3 to deuterated 20:4n6 and 20:5n3, respectively. Our findings show that the feline brain is a unique site of 22:6n3 production in this species, therefore, we are investigating the effects of chronic alcohol exposure on the brain's lipid composition and 22:6n3 formation. Our recent studies indicate specific fats in the diet regulate the synthesis of polyunsaturated fatty acids in carnivores and non-human primates. We have initiated human trials to investigate the effects of diet, and alcohol withdrawal on essential fatty acid metabolism.

去饱和和延伸是修饰的必要步骤 必需脂肪酸 (EFA)、亚油酸 (18:2n6) 和亚麻酸 (18:3n3) 酸，花生四烯酸（20:4n6）和二十二碳六烯酸（22:6n3）， 分别。 后两种脂肪酸的水平降低 动物血细胞、肝脏和大脑中的乙醇消耗。 我们有 研究表明，破坏必需脂肪的机制 这些组织中的酸水平部分是由于抑制 通过酒精对 18 碳必需脂肪酸进行延伸/去饱和。 一个 稳定同位素气相色谱-质谱（GC-MS）方法 已开发出允许对这些过程进行体内检查的技术。 该方法提高了大型动物研究的灵敏度。 对小鼠、大鼠、猫和恒河猴的研究表明，所有 哺乳动物具有伸长和去饱和能力，并且其后代产品 可以在血液供应中进行监测。 猫科动物，已被赋予 饮酒 14 周，20:4n6 减少 80%， 肝脏和血液中的二十碳五烯酸 (20:5n3) 与 氘代 18:2n6 和 18:3n3 向氘代的代谢减少 分别为 20:4n6 和 20:5n3。 我们的研究结果表明，猫科动物的大脑 是该物种中 22:6n3 生产的独特位点，因此，我们 研究长期饮酒对大脑脂质的影响 组成和22:6n3形成。 我们最近的研究表明具体 饮食中的脂肪调节多不饱和脂肪酸的合成 食肉动物和非人类灵长类动物。 我们已经启动人体试验 研究饮食和戒酒对必需脂肪的影响 酸代谢。