Cardiac mitochondrial respiration in two rodent models of obesity

Simple item page
dc.contributor.advisorEssop, Faadielen_ZA
dc.contributor.authorChan, Wing Yin Annaen_ZA
dc.date.accessioned2014-07-29T09:02:56Z
dc.date.available2014-07-29T09:02:56Z
dc.date.issued2006en_ZA
dc.descriptionIncludes bibliographical references (leaves 95-107)
dc.description.abstractObesity 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.en_ZA
dc.identifier.apacitationChan, W. Y. A. (2006). <i>Cardiac mitochondrial respiration in two rodent models of obesity</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/3371en_ZA
dc.identifier.chicagocitationChan, Wing Yin Anna. <i>"Cardiac mitochondrial respiration in two rodent models of obesity."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2006. http://hdl.handle.net/11427/3371en_ZA
dc.identifier.citationChan, W. 2006. Cardiac mitochondrial respiration in two rodent models of obesity. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Chan, Wing Yin Anna AB - 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. DA - 2006 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - Cardiac mitochondrial respiration in two rodent models of obesity TI - Cardiac mitochondrial respiration in two rodent models of obesity UR - http://hdl.handle.net/11427/3371 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3371
dc.identifier.vancouvercitationChan WYA. Cardiac mitochondrial respiration in two rodent models of obesity. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2006 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3371en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedicineen_ZA
dc.titleCardiac mitochondrial respiration in two rodent models of obesityen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
thesis_hsf_2006_chan_w_y_a (1).pdf
Size:
21.61 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Masters