| Summary: | Obese individuals are at greater risk of various comorbidities including cancer, diabetes, and cardiovascular disease (CVD). Endocrine imbalances and dyslipidemia are likely contributors to the etiology of these diseases in obese individuals. === The objectives of this research project were: (1) to determine the effectiveness of a self-selected diet and exercise weight loss (WtL) protocol in overweight and obese women; (2) to investigate the effects of moderate WtL on hormones associated with the regulation of energy balance, blood lipid levels, and low density lipoprotein (LDL) particle size; (3) to characterize changes in cholesterol metabolism as a result of moderate WtL through an examination of factors that likely play a role in its modulation, specifically body composition and single nucleotide polymorphisms (SNP) in ATP binding cassette (ABC)G5 and ABCG8 transporter. === In carrying out these objectives, 35 women were included in a 24-week WtL trial. Hormone, lipids, and cholesterol metabolism were assessed at the end of two stabilization periods. During these periods, body composition was also measured via magnetic resonance imaging (MRI). WtL was achieved through a 20% decrease in energy intake using diet combined with a 10% increase in energy expenditure through physical activity. === Overall, participants lost an average of 11.7+/-2.5 kg. WtL resulted in improvements in blood lipid risk factors of CVD with minimal effect on LDL particle size. No associations were found between leptin, ghrelin, adiponectin, and insulin. Cholesterol synthesis decreased as a result of WtL, while cholesterol absorption and turnover did not change. Despite an absence of change in turnover, increases were predicted by decreases in visceral adipose tissue, and decreases in cholesterol absorption were associated with losses in total and upper body skeletal muscle. This study also showed that changes in cholesterol concentrations and metabolism after WtL are associated with SNPs in ABCG5 and ABCG8 genes. === These findings suggest that hormones important in the regulation of energy homeostasis may exert their effects independently. Moderate WtL results in cardioprotective changes in blood cholesterol levels primarily due to changes in cholesterol synthesis. These findings also indicate that the responsiveness of blood cholesterol levels and metabolism to weight loss is modulated by changes in body composition and SNPs in ABCG5 and ABCG8.
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