Investigating the Relationship Between Early Life Exposure to Dietary Polyunsaturated Fatty Acids and Markers of Inflammation in Healthy Populations

Early exposure to dietary fats is thought to influence long-term health outcomes, particularly risk for developing a number of chronic diseases later in life. These include obesity, cardiovascular disease, diabetes, and certain types of cancers. A common risk factor among these diseases is chronic inflammation, which can be heavily influenced by diet and lifestyle factors. Specifically, it is thought that individual n-3 and n-6 polyunsaturated fatty acids (PUFA), both in the diet and circulating in the blood, may play a role mitigating or exacerbating the effects of chronic inflammation, beginning in very early life. Studies have shown that there is a role of n-3 PUFA in reducing chronic inflammation and associated chronic disease outcomes. However, the majority of these studies examine the role of n-3 PUFA on disease prognosis and treatment, rather than disease prevention. Few studies have examined the role of dietary PUFA in reducing disease risk and prevention of chronic disease using dietary intervention with dietary PUFA in very early life. This thesis aimed to investigate the associations between early life exposure to PUFA and markers associated with chronic inflammation in human and experimental mouse studies. The findings of thesis revealed that intakes of n-3 PUFA are low in very young children and that circulating levels of EPA and DHA in the plasma of these children are associated with increased ii total dietary inflammatory potential, a measure that has been associated with increased levels of circulating inflammatory markers. In preclinical studies, this thesis found that in utero exposure to diets high in n-6 and n-3 PUFA resulted in significant differential incorporation of dietary PUFA into spleen and liver tissues, but did not impact the expression of enzymes involved in the production of pro-inflammatory mediators. This finding may be clinically relevant to humans, as increased levels of n-6 and n-3 PUFA in these tissues have been shown to impact inflammatory and immune response in individuals who are presented with an immunological challenge. Collectively, these findings highlight the importance of continued efforts to increase intakes of n- 3 PUFA in the diets of young children, as this is when early dietary and lifestyle habits are formed. As such, early dietary intervention with n-3 PUFA may have the potential to improve long-term health outcomes, particularly risk for developing chronic inflammation and a number of common chronic diseases later in life.