Oxidized Cyclic Fatty Acid Monomers From Polyunsaturated Oils: Formation, Structures and Potential Biological Activities

环状脂肪酸单体(CFAM)是人类饮食的一部分。在油炸和精炼等热加工过程中，它们在食用油中含量较低。尽管有记载的负面生物活性及其在加工食品中的存在，但CFAM仍然没有得到充分的调查，解决这种情况是当务之急。该研究计划的长期目标是1)很好地了解油炸温度下脂肪分子转化所涉及的反应机理，并开发控制它们的方法；2)评估它们的潜在生物活性；3)探索它们在不同应用中的附加值。为了实现我们的长期目标，在过去的5年里，我们研究了CFAM的形成动力学；合成了一种标记的(2H)CFAM，并证明了食品中最丰富的CFAM会导致甘油三酯在肝脏中的积累(脂肪肝)，改变肝酶的活性，最重要的是，比起加拿大已被禁止的工业反式脂肪，CFAM是更有效的致动脉粥样硬化剂！我们还进行了两项初步研究：1)由于低水平的CFAM扰乱肝脏酶代谢，我们假设含有CFAM的加热PUFA油可能影响微生物的酶活性并具有抗菌作用：我们观察到对四种细菌的生长抑制；2)我们假设多不饱和CFAM可以很容易地氧化成CFAM-Ox：我们发现CFAM的异构体氧化速度快于亚油酸，支持油中CFAM的水平被低估，因为它们排除了CFAM-Ox。我们的这些工作成果是朝着我们的长期目标取得的非常重大的进展，现在已经为开展CFAM-Ox的生产、表征和生物活性的研究铺平了道路。我们推测，CFAM-Ox这类未知的新产物，其结构可能类似于必需的信号分子前列腺素、植物前列腺素和植物呋喃，可能在痕量水平上干扰生物系统中的关键反应和信号转导。未来5年的具体目标是：1)总结我们关于在油炸温度下形成CFAM的机制的研究；2)测定加热/煎炸油中可能的CFAM-Ox的水平并进行其化学表征；以及3)启动对CFAM-Ox的生物活性的评估，如其抗菌潜力。从这项研究中获得的知识将有助于更好地了解食品油炸过程中CFAM和CFAM-Ox形成的化学机制和动力学，制定控制或延缓这些降解反应的策略，并评估它们的潜在生物活性。这项计划将有助于培训4-5名研究生，在脂肪和油类化学和脂肪组学，这是一个对加拿大具有战略重要性的领域。

Cyclic fatty acid monomers (CFAM) are part of the human diet. They are formed at low levels in edible oils during thermal processing operations such as frying, and refining. Despite documented negative biological acvitivies and their presence in processed foods, CFAMs remain underinvestigated and it is imperative to address this situation. The long term goals of the research program are 1) to gain a good understanding of reaction mechanisms involved in the transformation of lipid molecules at frying temperatures and develop methods for their control; 2) to assess their potential bioactivities; and 3) to explore their value-addition in different applications. Moving towards our long term goals, we have, in the past 5 years, studied the formation kinetics of CFAMs; synthesized a labeled (2H) CFAM, and demonstrated that the most abundant CFAMs in foods cause an accumulation of triglycerides in the liver (fatty liver), alter the activities of liver enzymes, and, most importantly, are much more potent proatherogenic agents than industrial trans fats which have been banned in Canada! We also conducted two preliminary studies: 1) since low levels of CFAM disrupt the liver enzyme metabolism, we hypothesized that heated PUFA oils containing CFAM may affect enzymatic activities of microbes and have antimicrobial effects: we observed a growth inhibition on four bacteria; 2) we hypothesized that polyunsaturated CFAM can oxidize readily into CFAM-Ox: we found that isomers of CFAMs oxidize faster than linoleic acid, supporting that levels of CFAM in oils are underestimated as they exclude CFAM-Ox. These results from our work constitute a very significant progress towards our long term goal and have now paved the way to undertake studies on the production, characterization and biological activities of CFAM-Ox. We hypothesize that this potent unknown new class of products, the CFAM-Ox, whose structures may be similar to those of essential signal molecules prostanoids, phytoprostans and phytofurans, could, at trace levels, interfere with critical reactions and signal transduction in biological systems. The specific objectives for the next 5 years are: 1) To conclude our studies on the mechanisms by which CFAMs are formed at frying temperatures; 2) To determine the level of the putative CFAM-Ox in heated/frying oils and carry out their chemical characterization; and 3) To initiate the evaluation of bioactivities of CFAM-Ox such as their antimicrobial potential. Knowledge gained from this research will lead to a better understanding of the chemical mechanisms and the kinetics involved in the formation of CFAM and CFAM-Ox during the frying of foods; to the development of strategies to control or retard those degradative reactions; and to the evaluation of their potential biological activities. This program will contribute to the training for 4-5 graduate students, in Chemistry of Fats and Oils and Lipidomics, an area of strategic importance to Canada.