Obesity is a well recognized public health problem in the U.S. and the magnitude of excess weight isgreater among racial/ethnic minority populations such as Native Hawaiians (NHs) and Pacific Peoples (PPs).In Hawai'i, the overall percentage reported to be overweight or obese was 50% in 2003. Concurrent with theepidemic of overweight and obesity in the U.S., is the alarming rates of obesity-related diseases such asdiabetes mellitus. NHs and Filipino (who are PPs) populations have diabetes at rates of ~8.0%.Recent evidence has shown organ specific mitochondrial (mt) energetic alterations in individualsdiagnosed with Type II diabetes and/or obesity. Insulin resistance in the elderly and in children of parentswith Type II diabetes has been associated with decreased ATP production in skeletal muscle. Similardecreases in ATP levels have been observed in the livers of obese individuals compared to non-obese.Additionally, subsarcolemmal muscle mt are decreased in either obese or diabetic individuals compared tolean subjects. This corresponds with decreases in mtDNA and oxidative phosphorylation enzyme activities.Furthermore, depletion of mtDNA has been noted in peripheral blood mononuclear cells (PBMCs) of healthyinsulin resistant young adults. Additionally, Type II diabetes and/or obesity has been associated withincreased mt oxidative stress in PBMCs and plasma. Currently, there is no minimally invasive method tostudy mt dysfunction in diabetes and/or obesity.We hypothesize that a mitochondrial phenotype of diabetes and/or obesity may be studied in PBMCs ofindividuals. We also hypothesize that a pre-diabetic phenotype may be detectable in PBMCs of insulinresistant individuals. In a longitudinal approach, we propose to study mitochondrial function in PBMCs in100 obese NHs and PPs undergoing a 16-week weight loss intervention at baseline, immediately followingthe intervention (week 16) and after 1-year of follow-up. We believe that mitochondrial parameters willimprove as a result of weight-loss and correspond to an improvement in the pre-diabetic phenotype.We intend to evaluate at baseline, 4 months, and 16 months PBMC mtDNA copies/cell, OXPHOSprotein/enzyme activity using a novel immunological assay, and mitochondrial oxidative damage (8-oxodeoxyguanine). Phenotype characteristics will be obtained by evaluating body mass index (BMI) andmetabolic parameters (fasting insulin, glucose, and cholesterol).The significance of the proposed study lies in the fact that obesity and diabetes are major public healthissues particularly in minority populations. Understanding the mechanisms contributing to obesity anddiabetes may provide clues to intervention and treatment to improve morbidity and mortality.
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