Effect of maternal dietary Omega-6 to Omega-3 polyunsaturated fatty acid ratios on lipid and lipoprotein metabolism of the offspring of C57BL/6 mice

Randunu, Raniru Sergaevna (2012) Effect of maternal dietary Omega-6 to Omega-3 polyunsaturated fatty acid ratios on lipid and lipoprotein metabolism of the offspring of C57BL/6 mice. Masters thesis, Memorial University of Newfoundland.

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Abstract

Dietary fats are a major component of our diet; the quantity and the quality of dietary fats have been associated with the risk of cardiovascular disease (CVD). Epidemiological and laboratory studies have shown that increased consumption of saturated fatty acids (SFA) are associated with an increased risk of CVD, whereas consumption of polyunsaturated fatty acids (PUFA) are associated with reducing the risk of CVD. The current recommendations to replace SFA with PUFA have led to an increased consumption of omega-6 (n-6) PUFA, shifting n-6 to omega-3 (n-3) PUFA ratio from the 2-3:1 in the diets of early hunter-gatherers to 25:1 in the Western diet, which may raise the risk of CVD. One of the objectives of this thesis was to investigate the effect of various dietary n-6 to n-3 PUFA ratios on the regulation of lipid and lipoprotein metabolism using C57BL/6 mice as an animal model. The findings showed significant alterations in biochemical parameters of C57BL/6 mice fed diets varying in n-6 to n-3 PUFA ratios, which formed the basis for the maternal nutrition study. It is now apparent that maternal diet during gestation and lactation may predispose the offspring to CVD in later life. According to the 'developmental origins of health and disease' hypothesis, foetus responds to the nutritional environment by undergoing a series of irreversible adaptations that predisposes the offspring to metabolic disorders in later life. Given the health benefits of maintaining a proper ratio of dietary n-6 to n-3 PUFA, it was of interest to understand the role of altered maternal dietary n-6 to n-3 PUFA ratio on the regulation of lipid and lipoprotein metabolism in the offspring of C57BL/6 mice at weaning. Offspring at weaning were selected to isolate the effects of pre-weaning diet, excluding the post weaning diet, on the offspring's lipid and lipoprotein metabolism. The C57BL/6 mice were selected for the current study as these have been already established as an animal model in our laboratory to study 'in utero' programming of lipid and lipoprotein metabolism in the offspring. -- In the one month feeding study, female C57BL/6 mice were fed a diet containing 20% w/w fat with n-6 to n-3 PUFA ratio of either 5:1, 15:1 or 30:1 to establish the effect on the regulation of lipid and lipoprotein metabolism. Mice were sacrificed after one month and various metabolic parameters were measured. Feeding diets with varying n-6 to n-3 PUFA ratios to C57BL/6 mice led to the incorporation of dietary fatty acids in red blood cell (RBC) phospholipids (PL), and also altered the regulation of lipid and lipoprotein metabolism. In the maternal nutrition study, 8 week old female C57BL/6 mice were fed a diet containing 20% w/w fat with n-6 to n-3 PUFA ratios of either 5:1, 15:1 or 30:1 for two weeks before mating, during gestation and lactation. Both male and female offspring from each dietary group (n =10/group) were sacrificed at weaning and various metabolic parameters were measured. A higher n-6 to n-3 PUFA ratio in the maternal diet of C57BL/6 mice led to higher plasma lipid and lipoprotein concentrations compared to a lower ratio in the offspring at weaning. Moreover the effect of maternal diet was gender specific. In conclusion, a maternal diet high in n-6 to n-3 PUFA ratio resulted in higher levels of lipid and lipoproteins in the offspring at weaning, which may be associated with an increase risk of CVD in later life.

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