Dietary fat intake during pre- and post-weaning time period and its association with the onset of cardiovascular diseas in the offspring

Chechi, Kanta (2010) Dietary fat intake during pre- and post-weaning time period and its association with the onset of cardiovascular diseas in the offspring. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

The 'fetal origins' of cardiovascular disease (CVD) hypothesis proposes that maternal nutritional environment during pregnancy can play an important role in determining the cardiovascular health of an individual in adult life. A typical Western diet is rich in dietary fats, a fact that has been linked to the increased prevalence of CVD. In addition to the quantity of fat, the quality of fat is also known to affect the development of CVD. Whilst an increased consumption of saturated fatty acids (SFA) has been associated with higher incidence of CVD, a diet rich in polyunsaturated fatty acids (PUFA) has been suggested to lower the risk of developing CVD. Considering that nutrition patterns are shifting towards a higher-fat Western diet globally, it is of interest to understand the role of a high-fat maternal diet in the fetal origins of CVD. The current thesis was designed to understand the role of the quantity, as well as the quality, of maternal dietary fat intake during pregnancy, in the fetal origins of CVD in the adult offspring. In addition, the role of interaction between the pre- and post-natal dietary fat intake on the offspring health was assessed. Early programming experiments were conducted using C57B1/6 mice, which have been extensively used as an animal model to investigate the dietary fat-mediated regulation of lipid metabolism. Lipid metabolism and aortic vascular function were chosen as the study outcomes to estimate the risk of developing CVD in the offspring. Results indicated that a high-fat maternal diet rich in SFA (lard) was associated with a reduced expression of hepatic low-density lipoprotein (LDL)-receptor and a higher concentration of LDL-cholesterol in the offspring. On the other hand, a high-fat maternal diet rich n-6 PUFA (safflower oil) was associated with higher mRNA expression of hepatic lecithin: cholesterol acyltransferase and higher concentration of high-density lipoprotein-cholesterol in the offspring. The high-fat maternal diet, irrespective of the type of fat, however was associated with reduced aortic contractile reactivity towards KC1, phenylephrine and thromboxane mimetic U44619, in the female offspring. In addition, significant interaction of pre- and post-weaning diets was reported for various outcomes studied in the offspring, suggesting the importance of both prenatal and postnatal environments in regulating the offspring cardiovascular health. -- In a separate study, the effects of n-3 PUFA-rich flax oil feeding were assessed on various parameters associated with metabolic syndrome, using the SHR/NDmcr-cp rat model. Flax oil feeding was associated with significantly lower hepatic triglycerides and cholesterol concentrations in the obese rats. In addition, flax oil feeding was associated with lower plasma insulin concentrations and oxidative stress in the obese rats. An up regulation in the hepatic expression of peroxisome-proliferator activated receptor-γ (PPAR-γ) was found to be negatively correlated with the hepatic TG and cholesterol concentrations in the obese rats, thus pointing towards the activation of PPAR-γ dependent pathways behind the hepatic lipid-lowering effects of flax oil supplementation. -- Taken together, the results presented in the current thesis support the role for the quantity and the quality, of dietary fats consumed during pre- and post-weaning time periods, on the development of key parameters associated with the onset of CVD.

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