High Temperature Degradation of Fatty Acids: Cyclic Fatty Acid Monomers From Frying Oils, Their Formation and Potential Health Impacts

膳食脂肪是人类饮食中必不可少的一部分，因为它们是能量的集中来源和必需脂肪酸(FA)的主要来源，总的来说，加拿大人认识到多不饱和脂肪酸的有益健康属性。多年来，他们对油炸脂肪和油的消耗量一直在增加，这是因为尽管低脂肪/无脂肪饮食趋势，他们的饮食习惯发生了变化，偏爱油炸食品。*不饱和植物油加热导致热分解和氧化反应，导致降解产物，如反式和含氧脂肪酸、低聚物和环状脂肪酸单体(CFAM)的形成。从消费者健康和食品工业的运营经济的角度来看，降解产品令人严重关切，必须解决这一问题。因此，该研究计划的目标是深入了解在油炸温度下导致脂肪分子分解的化学反应机制，这将使开发控制这些恶化反应的方法成为可能，并评估其潜在的有害代谢影响。*我们已经证明，脂肪酸中CFAM的形成和共轭体系的重排是高温下周电子反应的结果。随后，我们对α-亚麻酸(Ln)生成CFAM的动力学进行了研究，以了解其反应机理，并确定了形成5元环和6元环CFAM的关键中间体。特别值得注意的是，我们合成了一种标记的(氢；2H)和位置特定的6元环CFAM，并在动物模型中对该分子的代谢组学进行了研究，该动物模型饲喂了低水平(总脂的0.5%)的饲料。无论是尿液的成分还是血浆的成分都可以区分治疗组和对照组，在对照组中，喂食CFAM的动物血浆中的肉碱和溶血磷脂水平显著降低，这是脂质生物合成/使用的指标。我们还在尿样和血浆样本中发现了许多CFAM的代谢物，这表明CFAM经历了伯氧化，通常以葡萄糖醛酸、硫酸盐和硝酸盐的结合物的形式被消除。这项工作的结果是朝着我们的长期目标取得的重大进展，现在已经为开展一类来自煎炸油的新型氧化产物-氧化CFAM(CFAM-Ox)的产生、表征和代谢影响的研究铺平了道路。*我们假设CFAM-Ox在煎炸油中形成，并可能具有有害的代谢影响，即使在微量水平上也是如此。这类鲜为人知的氧化化合物是从煎炸油中产生的，可以表现出与前列腺素类似的某些活性，因此，它们可以干扰关键的生物反应以及导致生理变化和疾病发生的信号转导。

Dietary fats are an essential part of the human diet since they are a concentrated source of energy and a major source of essential fatty acids (FA), and in general, Canadians recognize the beneficial health attributes of polyunsaturated FA. Their consumption of fats and oils for frying has been increasing over the years, because of changes in the eating habits favoring fried foods, notwithstanding the low-fat/no-fat diet trend.***Heating of unsaturated vegetable oils results in thermolytic and oxydative reactions leading to the formation of degradation products such as trans and oxygenated FA, oligomers, and cyclic fatty acid monomers (CFAM). The degradation products are of serious concern from the standpoints of consumer health as well as the economics of operation for the food industry, and it is imperative to address this situation. Thus, the objectives of the research program are to gain a good understanding of the chemical reaction mechanisms leading to the decomposition of lipid molecules at frying temperatures, which would enable the development of methods to control those deteriorative reactions; and to assess their potential harmful metabolic effects.***We have shown that the formation of CFAM and the rearrangement of conjugated systems in FAs result from peri-electronic reactions at high temperatures. Subsequently, we studied the kinetics of the formation of CFAM from a-linolenic acid (Ln) in order to understand the mechanisms, and identify the key intermediates in the formation of both 5- and 6-membered ring CFAM. Of particular note are our synthesis of a labeled (deuterium; 2H) and position-specific 6-membered ring CFAM, and metabolomics of this molecule in an animal model fed a diet containing low level (0.5% of total lipids). Either the composition of urine or the plasma alone could discriminate between the treated and control groups, where the levels of carnitines and lysophospholipids, indicators of lipid biosynthesis/use, were significantly reduced in the plasma of animals fed CFAM. We have also identified many metabolites of CFAM in both urine and plasma samples that indicated that CFAM undergo ß-oxidation and are typically eliminated as glucuronide, sulphate and nitrate conjugates. The results of this work constitute a significant progress towards our long term goal and have now paved the way to undertake studies on the production, characterization and metabolic effects of a potent new class of oxidation products from frying oils, the oxidized CFAMs (CFAM-Ox).***We hypothesize that CFAM-Ox are formed in frying oils and may be have harmful metabolic effects, even at trace levels. This little known class of oxidized compounds, produced from frying oils, could exhibit certain analogous activities as those of the prostanoids, and consequently, they could interfere with critical biological reactions as well as signal transduction leading to altered physiology and incidence of diseases.