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

环脂肪酸单体（CFAM）是人类饮食的一部分。它们在热加工操作（如油炸和精炼）期间在食用油中以低水平形成。尽管有文件记载的负面生物活性及其在加工食品中的存在，CFAM仍然没有得到充分的调查，必须解决这一问题。该研究计划的长期目标是：1）充分了解油炸温度下脂质分子转化的反应机制，并开发控制方法; 2）评估其潜在的生物活性; 3）探索其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;合成了标记的（2 H）CFAM，并证明食物中最丰富的CFAM会导致肝脏中甘油三酯的积累（脂肪肝），改变肝酶的活性，最重要的是，是更有效的促动脉粥样硬化剂比工业反式脂肪已被禁止在加拿大！我们还进行了两项初步研究：1）由于低水平的CFAM会破坏肝脏酶代谢，我们假设含有CFAM的加热PUFA油可能会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可以容易地氧化成CFAM-Ox：我们发现CFAM的异构体比亚油酸氧化得更快，这支持了油中CFAM的水平被低估，因为它们排除了CFAM-Ox。我们工作的这些结果构成了我们长期目标的一个非常重要的进展，现在已经为进行CFAM-Ox的生产，表征和生物活性的研究铺平了道路。我们假设，这种有效的未知的新一类产品，CFAM-Ox，其结构可能类似于那些基本的信号分子前列腺素类，植物前列腺素和植物呋喃，可以在痕量水平，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）总结我们对在油炸温度下形成CFAMs的机制的研究; 2）确定加热/油炸油中假定CFAM-Ox的水平并进行化学表征; 3）开始评估CFAM-Ox的生物活性，例如其抗菌潜力。从这项研究中获得的知识将导致更好地理解的化学机制和动力学参与形成CFAM和CFAM-Ox在油炸食品;战略的发展，以控制或延缓这些降解反应;并评估其潜在的生物活性。该计划将有助于培训4-5名研究生，在脂肪和油脂化学和脂质组学，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.