Omega-3 Fatty Acids in the Development and Progression of Obesity

With the growing global prevalence of overweight and obesity, there is a need for further understanding of the physiological mechanisms underlying increases in adiposity. Primarily resulting from an imbalance between energy consumed and energy expended, obesity is independently associated with altered levels of adipose hormones including decreased adiponectin and increased leptin levels. Significant correlations have been observed between obesity and dietary patterns. Omitting meals such as breakfast and to slightly lesser degree lunch have been correlated with increased susceptibility to obesity in the absence of significant correlations to total energy intake. Lipids have a greater energy density per gram than carbohydrates or proteins such that dietary intake of saturated and total fatty acids have been shown to contribute to the development of obesity and insulin resistance. Conversely, diets high in omega-3 fatty acids have been correlated with the prevention of obesity and the subsequent development of chronic disease sequalae. Omega-3 derived effects on plasma adiponectin and leptin levels have been postulated as contributing to these effects. This thesis aims to explore dietary, hormonal and physiological predictors of regulatory hormones associated with the development of obesity and insulin resistance in non-diabetic overweight and obese adults. As results of previous studies exploring the effects of omega-3 supplementation on adipokine levels have been inconsistent, this thesis also explores the predictors of change in these hormones associated with omega-3 supplementation. Given the importance of understanding and evaluating dietary intake in the management of obesity, consideration has also been given to the validity of dietary reporting and screening methods in this cohort. A phase 1, comparative clinical trial was conducted at the Princess Alexandra Hospital, Brisbane. Forty participants were recruited (10 overweight and 30 obese). All participants were over 18 years of age, stable weight, non-diabetic, non-smokers and generally healthy. Anthropometric measures and fasting blood samples were taken at baseline and following 8 weeks of supplementation with 2g/day of omega-3. Fasting blood samples were taken before and after supplementation to quantify adiponectin, leptin, markers of insulin sensitivity, liver and kidney function parameters, parameters as well as blood lipids. Participants were also asked to completed questionnaires related to physical activity, fatigue and dietary intake at each time point. Analysis of baseline results demonstrated that adiponectin levels were inversely correlated with selected liver enzymes, indicating potential links to fatty acid deposition in the liver or liver. Conversely baseline leptin levels were best predicted by measures of adiposity but not liver enzymes. Each of these variables, along with blood lipids may serve as potential future therapeutic targets for the prevention of management of obesity and related co-morbidities. Omega-3 derived changes in circulating adiponectin levels demonstrated no significant correlation to anthropometric measures, markers of insulin sensitivity or blood lipids. Omega-3 derived changes in leptin levels were positively correlated with BMI and inversely correlated with selected renal function parameters providing insight into inconsistencies in the results of previous studies which have assessed the effects of omega-3 on this hormone. Baseline levels of glycosylated haemoglobin and insulin were positively correlated with selected liver function markers, reinforcing the integral role of liver function in development of IR. Additionally, analysis of 72 hour dietary intake questionnaires revealed a clear bias for under-reporting within this population. Overall, these results highlighted a number of potential therapeutic targets for the prevention of obesity and insulin resistance, as well as the importance of (Body Mass Index) BMI and renal function parameters in determining omega-3 derived changes in plasma leptin levels. This thesis will report the complete findings of these investigations, incorporating a combination of manuscripts, either published, in press or currently under review. These findings will then be drawn together in a comprehensive discussion, highlighting significant findings, clinical implications and future directions.