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Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes. / Danielle Alice Jones

Swansea University Author: Danielle Alice Jones

Abstract

In the past 30 years the prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus (T2DM) and other co-morbidities. Visceral adipose tissue is believed to play a vital role in these conditions, but underlying mechanisms remain unclear. A close associati...

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Published: 2013
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42244
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first_indexed 2018-08-02T18:54:14Z
last_indexed 2019-10-21T16:47:28Z
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spelling 2018-08-29T14:55:38.1251639 v2 42244 2018-08-02 Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes. 7691cc09bb4f6a18ce3661ee3a1c1cd2 NULL Danielle Alice Jones Danielle Alice Jones true true 2018-08-02 In the past 30 years the prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus (T2DM) and other co-morbidities. Visceral adipose tissue is believed to play a vital role in these conditions, but underlying mechanisms remain unclear. A close association exists between obesity, diabetes and oxidative stress, resulting in increased reactive oxygen species formation. The experiments in this thesis address this by searching for possible biochemical changes which may be specific for the onset of obesity related T2DM, as well as looking for genetic alterations at molecular and gene expression levels. This thesis also explored various techniques such as polymerase chain reaction (PCR), colorimetric assays and real-time RT-PCR. The aim was to investigate the role of adipose tissue in obesity and T2DM, focusing on markers of oxidative stress and gene expression in human visceral adipose tissue from subjects categorised as lean, obese and obese with T2DM. This cross-sectional study measured two markers of oxidative stress, two markers of DNA damage, gene expression analysis and identification of genes associated with T2DM and obesity. Specific gene sequencing was carried out on the glutathione reductase gene to determine possible gene variants. Results showed a paradoxical decrease in adipose markers of oxidative stress in subjects with obesity and T2DM. There appeared to be a protective mechanism in these subjects, displaying reduced levels of oxidative stress compared to other groups. This could be due to a significant proportion of these subjects being on ACE inhibitor and statin therapy, which may be confounding results and minimising the effects of the oxidative burden. Additionally, the same subjects showed an increased expression of the glutathione reductase gene. It is difficult to conclude if the decreased levels of oxidative stress in these subjects were a result of the increased glutathione reductase expression in the visceral adipose tissue or if there remains an unseen factor influencing the dramatic expression change seen in this group of subjects. No glutathione reductase gene variants were identified in these samples. This analysis highlighted that within this sample set, the impact of oxidative stress is in fact reversible as the antioxidant capacity in these subjects is evident, and in combination with correct drug therapy it may be possible to combat oxidative burden and reduce the subsequent damage inflicted upon the cells. E-Thesis Biochemistry. 31 12 2013 2013-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T14:55:38.1251639 2018-08-02T16:24:28.5421834 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Danielle Alice Jones NULL 1 0042244-02082018162439.pdf 10797952.pdf 2018-08-02T16:24:39.3370000 Output 11703836 application/pdf E-Thesis true 2018-08-02T16:24:39.3370000 false
title Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
spellingShingle Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
Danielle Alice Jones
title_short Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
title_full Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
title_fullStr Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
title_full_unstemmed Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
title_sort Adipose tissue as a mediator of inflammation and oxidative cellular damage in obesity and type 2 diabetes.
author_id_str_mv 7691cc09bb4f6a18ce3661ee3a1c1cd2
author_id_fullname_str_mv 7691cc09bb4f6a18ce3661ee3a1c1cd2_***_Danielle Alice Jones
author Danielle Alice Jones
author2 Danielle Alice Jones
format E-Thesis
publishDate 2013
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description In the past 30 years the prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus (T2DM) and other co-morbidities. Visceral adipose tissue is believed to play a vital role in these conditions, but underlying mechanisms remain unclear. A close association exists between obesity, diabetes and oxidative stress, resulting in increased reactive oxygen species formation. The experiments in this thesis address this by searching for possible biochemical changes which may be specific for the onset of obesity related T2DM, as well as looking for genetic alterations at molecular and gene expression levels. This thesis also explored various techniques such as polymerase chain reaction (PCR), colorimetric assays and real-time RT-PCR. The aim was to investigate the role of adipose tissue in obesity and T2DM, focusing on markers of oxidative stress and gene expression in human visceral adipose tissue from subjects categorised as lean, obese and obese with T2DM. This cross-sectional study measured two markers of oxidative stress, two markers of DNA damage, gene expression analysis and identification of genes associated with T2DM and obesity. Specific gene sequencing was carried out on the glutathione reductase gene to determine possible gene variants. Results showed a paradoxical decrease in adipose markers of oxidative stress in subjects with obesity and T2DM. There appeared to be a protective mechanism in these subjects, displaying reduced levels of oxidative stress compared to other groups. This could be due to a significant proportion of these subjects being on ACE inhibitor and statin therapy, which may be confounding results and minimising the effects of the oxidative burden. Additionally, the same subjects showed an increased expression of the glutathione reductase gene. It is difficult to conclude if the decreased levels of oxidative stress in these subjects were a result of the increased glutathione reductase expression in the visceral adipose tissue or if there remains an unseen factor influencing the dramatic expression change seen in this group of subjects. No glutathione reductase gene variants were identified in these samples. This analysis highlighted that within this sample set, the impact of oxidative stress is in fact reversible as the antioxidant capacity in these subjects is evident, and in combination with correct drug therapy it may be possible to combat oxidative burden and reduce the subsequent damage inflicted upon the cells.
published_date 2013-12-31T03:52:35Z
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score 11.037603

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