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的重要组成部分，因为它们是能量的集中来源和必需脂肪酸（FA）的主要来源，一般来说，加拿大人认识到多不饱和脂肪酸的有益健康属性。近年来，尽管有低脂/无脂饮食的趋势，但由于饮食习惯的改变，他们对油炸食品的食用油脂的消费量一直在增加。 不饱和植物油的加热导致热解和氧化反应，导致形成降解产物，如反式和氧化FA、低聚物和环状脂肪酸单体（CFAM）。从消费者健康以及食品工业运营经济的角度来看，降解产物是一个严重的问题，必须解决这一问题。因此，该研究计划的目标是充分了解在油炸温度下导致脂质分子分解的化学反应机制，这将有助于开发控制这些恶化反应的方法;并评估其潜在的有害代谢影响。 我们已经表明，CFAM的形成和共轭系统的重排FAs的结果从在高温下的近电子反应。随后，我们研究了从α-亚麻酸（Ln）形成CFAM的动力学，以了解其机制，并确定形成5-和6-元环CFAM的关键中间体。特别值得注意的是，我们合成了标记的（氘; 2 H）和位置特异性的6元环CFAM，以及在喂食低水平（总脂质的0.5%）饮食的动物模型中该分子的代谢组学。无论是尿液或血浆的组合物单独可以区分处理组和对照组，其中的肉毒碱和溶血磷脂，脂质生物合成/使用的指标，水平显着降低，在动物的血浆中喂食CFAM。我们还在尿液和血浆样品中鉴定了CFAM的许多代谢物，表明CFAM发生β-氧化，通常以葡糖苷酸、硫酸盐和硝酸盐结合物的形式消除。这项工作的结果构成了我们的长期目标的一个重大进展，现在已经铺平了道路，进行研究的生产，表征和代谢作用的一个强大的新的一类氧化产品从煎炸油，氧化的CFAMs（CFAM-Ox）。 我们假设CFAM-Ox是在煎炸油中形成的，即使在痕量水平，也可能具有有害的代谢作用。这类鲜为人知的氧化化合物，从煎炸油中产生，可以表现出某些类似的活动，前列腺素类，因此，它们可以干扰关键的生物反应以及信号转导，导致改变生理和疾病的发病率。

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.