Effect of long-term consumption of oxidized polyunsaturated fatty acids on atherosclerotic lesion in LDL receptor knockout mice

• Autor(a) principal: Nogueira, Marina Sayuri
• Data de Publicação: 2020
• Tipo de documento: Tese
• Idioma: eng
• Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
• Texto Completo: https://www.teses.usp.br/teses/disponiveis/9/9132/tde-20122021-112905/
• topic: Aterosclerose; Atherosclerosis; Camundongo; Mice; Omega 3; Omega 3; Omega 6; Omega 6; Oxidação; Oxidation

Polyunsaturated fatty acids (PUFA) are susceptible to enzymatic and non-enzymatic oxidation, leading to the production of secondary compounds that present different physiological effects. Among the PUFA, the products formed from Omega 6 (n-6 FA) and Omega 3 (n-3 FA) fatty acids oxidation can modulate inflammation, dyslipidemia and oxidative stress preventing or reducing the atherosclerosis progression. In fact, the effect of chronic intake of edible oils containing products of polyunsaturated fatty acids oxidation (POPs) on atherosclerosis is still controversial. In general POPs from n-6 FA have a more pro-inflammatory profile than POPs from n-3 FA. Thus, the objective of this study was to compare the chronic intake of partially oxidized n-6 FA and n-3 FA rich oils on atherosclerosis biomarkers. Initially, six edible oils containing a higher amount of n-6 and n-3 FA were submitted to oxidative conditions, simulating the steps of transport, storage and consume. It was observed that oxidative reaction started in all oils since the first step and at the moment of consumption, some oxidative chemical markers were out the legal range suggested by the Official Agencies. In addition, it was possible to identify the type of secondary product formed from each precursor oil, providing a better information for oils quality control. After this step, fish and soybean oils were chosen as n-3 FA and n-6 FA rich oils, respectively. Using LDLr(-/-) mice, the effect of three oxidative levels of soybean oil was evaluated after 24 weeks of supplementation. Animals fed with the oil with the highest level of oxidation (fried and reused oil) showed no body weight gain, suggesting that POPs from soybean oil at this level could promote a browning effect on white adipose tissue by increasing UCP-1 expression. This group also showed the highest concentration of lipoproteins in plasma. However, these metabolic differences did not accelerate atherosclerosis in the animals. Finally, the effect of POPs from n-3 FA and n-6 FA oxidation were compared also using LDLr(-/-) mice as model for experimental atherosclerosis. Some alterations observed after n-3 FA supplementation, such as the increase of liver weight, IL-6, SONPC, 8-HETE and 15-F2-Isop and the decrease of BAT and glucose, were reversed by their POPs. In addition, POPs from n-6 FA caused increased of LDL and 5-HETE. As observed in the previous study, these metabolic alterations were not enough to prevent or accelerate atherosclerosis, as measured by histological analysis of the lesion size in the aorta. These results suggest that although a significant amount of POPs are being consumed by diet, their metabolic effects did not influence atherosclerotic plaques in the animal model. However, besides lesion area in the aortas, new studies should also evaluate the plaques stability.