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Adipose tissue derived factors in obesity, inflammation & energy homeostasis
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Kusminski, C. M. (2006) Adipose tissue derived factors in obesity, inflammation & energy homeostasis. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b2213519~S1
Abstract
Obesity is the foremost contributory factor in the progression to type 2 diabetes
mellitus (T2DM). Moreover, chronic inflammation, through activation of innate
immunity is proposed to link obesity, insulin resistance and T2DM. Adipose tissue,
traditionally considered a storage compartment for triglycerides, also functions as an
active endocrine organ. Adipocyte-secreted products, termed adipokines, may link
obesity-associated inflammation and insulin resistance. Adipokines exert multiple
effects on insulin sensitisation, glucose homeostasis, inflammatory processes or
central systems mediating energy expenditure. This thesis principally examined two
adipokines; resistin and adiponectin. Resistin and components of innate immunity
were assessed in human obesity. In-vitro analysis established that resistin was
expressed and secreted by human adipocytes. Furthermore, key factors in the innate
immune pathway were highly expressed in obese and T2DM adipose tissue. This
thesis further explored the pro-inflammatory actions of resistin in adipocytes. Resistin
stimulated the secretion of inflammatory cytokines from adipocytes and, the
expression of key intermediates of the innate immune and insulin signalling pathways.
Clinical studies entailed examination of resistin as a marker of inflammation in
childhood obesity. Serum analysis revealed gender-differences in resistin levels in
obese children. Furthermore, bacterial endotoxin correlated with several markers of
inflammation and cardiovascular disease; suggesting endotoxin as a contributor to
inflammation in childhood obesity. This thesis subsequently examined another
adipokine, adiponectin; considered to have a `ying-and-yang' relationship with
resistin. Studies explored a central role for adiponectin in energy homeostasis. Gelfiltration
liquid chromatography established that the adiponectin trimer was
predominant in human cerebrospinal fluid. Such identification of trimeric adiponectin
in vivo implicates the pharmacologically generated globular adiponectin in central
regulation of energy expenditure. In conclusion, resistin may serve as a pathogenic
pro-inflammatory factor, exacerbating inflammation within adipose tissue; potentially
contributing to the progression of obesity-driven T2DM. Alternatively, adiponectin
may have favourable central actions, influencing energy expenditure through its basic
trimeric form. Collectively, this thesis suggests that resistin and adiponectin, with a
range of opposing properties, may substantially affect whole-body metabolism.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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Library of Congress Subject Headings (LCSH): | Obesity, Non-insulin-dependent diabetes, Adipose tissues, Insulin resistance | ||||
Official Date: | December 2006 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Kumar, Sudhesh ; McTernan, P. G. (Philip G.) | ||||
Extent: | xv, 227 leaves | ||||
Language: | eng |
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