Obesity and dietary transition and their correlates with fatty acids and desaturases in three distinct populations

Adipose tissue has long been considered to be inert fat mass, and only in recent years has it's role as an active endocrine organ been recognized. Evidence from animal models suggests that adiposity along with insulin and diet could be an independent regulator of desaturases, which are keys in the biosynthesis of unsaturated fatty acids. Few epidemiological studies, however, have been performed in terms of the impact of adiposity on desaturases. Among the existing studies, there was no examination of whether the regulation would be independent of insulin action and dietary intake. The dietary transition among Canadian Indigenous Peoples and the consequent health transition including the emergence of obesity, have been well documented; however, it is not known how dietary and metabolic changes might affect the status of highly unsaturated n-3 fatty acids (HUFA n-3) that are implicated to be protective against chronic disease risk.The thesis work is composed of three studies. Study 1: The fatty acid composition of fasting plasma from 178 apparently healthy female adolescents from a Montreal gestational diabetes cohort was analyzed. Independent of dietary saturated fatty acids (SFA) intake and the level of insulin resistance, adiposity was demonstrated to be positively predictive of ∆9. The activity of ∆9 was, in turn, positively correlated with fasting plasma triglycerides (TG) and apoliproprotein B (Apo B). Study 2: The fatty acid composition of erythrocyte membranes from fasting blood was assessed from 168 Cree adults living in a single Cree community in northern Québec who were participating in a diabetes screening program. Inter-generational differences existed in terms of HUFA n-3 status. Adiposity was significantly but inversely associated with ∆5. The latter relationship was also observed among Cree with impaired fasting glucose, among whom insulin resistance was not a significant predictor of ∆5. Study 3: The fatty acid composition of erythrocyte membranes from fasting blood was determined from 2200 Inuit adults from Nunatsiavut, Nunavut and Inuvialuit Settlement Region (ISR) participating the International Polar Year Inuit Health Survey. Biochemical measures including of hemoglobin, serum ferritin and C-reactive protein (CRP) from 1528 Inuit adults were examined. Pronounced inter-generational and regional differences across Canadian Arctic regions regarding HUFA n-3 status were observed among Inuit. HUFA n-3 status was inversely related to SFA and TFA status. Additionally, HUFA n-3 status was associated with the presence of iron deficiency (ID) among Inuit; however, only a weak correlation was demonstrated indicating the need for confirmatory studies. In summary, this thesis work involving both female adolescents and the Cree and Inuit adult population has indicated that adiposity plays a more direct role in regulating fatty acid metabolism than previously realized via the demonstration of strong independent associations of adiposity with ∆5 and ∆9 desaturase activities. In terms of the Canadian indigenous peoples, the adverse effects on n-3 fatty acid metabolism mediated by relatively high prevalence of obesity could exacerbate chronic disease risk along with the diminishing consumption of HUFA n-3 rich traditional foods.

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