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Cardiac mitochondrial respiration in two rodent models of obesity

By Wing Yin Anna Chan

Abstract

Includes bibliographical references (leaves 95-107)Obesity is a major contributor to the global burden of disease and is closely associated with the development of type II diabetes. Recent studies have demonstrated that increased circulating free fatty acid (FFA) levels may have detrimental effects on the diabetic heart. In this study, we hypothesized that with obesity and obesity-induced insulin resistance/type II diabetes, increased FFA supply decreases cardiac mitochondrial bioenergetic capacity. Furthermore, we also hypothesized that females possess innate cardioprotective programs that will result in enhanced bioenergetic capacity compared to males. We examined our hypothesis employing two rodent models i.e. a) a rat model of diet-induced obesity and b) a transgenic (leptin receptor deficient) mouse model of obesity-induced type II diabetes. For the diabetic mouse model, we determined cardiac mitochondrial respiratory function in an age-dependent (10-12, 18-20 and 55-56 weeks) and gender-dependent (male versus female) manner. We found impaired mitochondrial respiratory capacity in obese rats in baseline and when isolated mitochondria were stressed by anoxia-reoxygenation. We speculate that this may be dure to reduced expression of mitochondrial respiratory chain complexes in the insulin resistant rat heart. For the mouse model and type II diabetes we found increased respiratory capacity at 10-12 weeks, thought to respresent the stage of metabolic syndrome, with no evidence of oxygen wastage or reduction of respiratory capacity. However, 18-20 week-old obese mice were unable to increase respiratory capacity. We also found increased mitochondrial ultrastructural damage and intracellular lipid accumulation in 18-20 week-old diabetic mouse hearts. We propose that this occurs as a result of a mismatch between increased FA uptake and decreased FA oxidative capacity

Topics: Medicine
Publisher: Department of Medicine
Year: 2006
OAI identifier: oai:open.uct.ac.za:11427/3371

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