Energy regulating hormones and the development of obesity and diabetes

Cahill, Farrell (2015) Energy regulating hormones and the development of obesity and diabetes. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Obesity, a complex multifactorial disease, is a serious public health concern due to numerous obesity-related comorbidities thought to result from various hormones in combination with lifestyle and environmental factors. At present, the role of only a fraction of the hormones involved in obesity have been well defined. The aims of this thesis were to investigate: 1) the association of appetite regulating hormones with obesity and obesity-related phenotypes in the Newfoundland and Labrador general population; 2) the response and interaction of appetite and energy regulating hormones on obesity development under a positive energy challenge; 3) the association of dietary magnesium intake with obesity and diabetes; 4) testing the validity of the body adiposity index (BAI) in a Caucasian population; 5) the association of BAI with cardiometabolic risk factors (CRF); 6) and the development of a novel and more accurate equation than body mass index (BMI)and BAI to evaluate adiposity. All of these were achieved using data from two different studies - the large scale, population-based CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study and an intervention-based, 7-day positive energy surplus study. We have discovered that circulating PYY (appetite suppressant) is not significantly associated with obesity status defined by either percent body fat (%BF) or BMI. However, circulating PYY was influenced by age, smoking, medication use, and menopausal status in women. We also sought to explore the endocrine response of normal-weight, overweight and obese individuals to a 7-day hypercaloric diet. We demonstrated that PYY increased in response to overfeeding, but was not associated with changes in insulin resistance and/or weight. We also found that adiponectin (insulin sensitizer) was not associated with obesity status but the significant increase in adiponectin, due to overfeeding, was significantly associated with insulin resistance. We also investigated the impact of dietary magnesium on obesity and obesity-related co-morbidities and found that higher dietary magnesium intake is associated with improved insulin sensitivity and this effect is particularly beneficial for overweight and obese individuals in the general population along with pre-menopausal women. Therefore, our data would suggest that the beneficial effects of magnesium intake are less sensitive among post-menopausal women. In addition, we explored the applicability of the BAI and found that it was a better estimate of adiposity than BMI in the non-obese Caucasian population. The BAI was also more closely associated with the relationship of %BF with CRFs than BMI. However, this association is significantly attenuated when assessing the influence of increasing BAI on CRFs amongst men and women examined separately. Lastly, we developed a sex-specific equation to overcome the gender related weakness of both BMI and BAI to predict adiposity. The body fat index (BFI) sex-specific equations we developed more accurately predict %BF than BMI and BAI in the general population and at various extremes of adiposity in men and women.

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