Creely, Steven J. (2009) Determining the mechanism contributing to sub-clinical inflammation in metabolic disease. PhD thesis, University of Warwick.

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Abstract

This thesis aims to investigate the role of innate immunity and the bacterial endotoxin lipopolysaccharide (LPS) in inflammation in adipose tissue. It attempts to do this by: 1) Describing the presence of Toll-like Receptors (TLR) in adipose tissue and adipocytes and their response to stimulation by LPS. It was demonstrated that both Toll-like receptor 2 and 4 were present in adipose tissue and that the receptors were present in greater amount in subjects with diabetes at a protein level and in subjects with obesity at both a RNA and protein level. It was also shown that these receptors responded to stimulation by LPS and that TLR-2 could be seen to be upregulated. 2) It was further shown that LPS induced production of inflammatory cytokines in cultured whole adipose tissue and adipocytes and caused downregulation of adiponectin in whole adiposes tissue. Blockade of NFκB in adipocytes was shown to regulate the levels of inflammatory cytokines produced and to differentially effect this levels dependent on whether whole adipose tissue or isolated adipocytes were cultured. 3) It was shown that LPS levels are significantly higher in the serum of T2DM subjects than controls and that these levels appeared to correlate with insulin. It was also seen that the LPS could be seen to correlate with inflammatory cytokines. It was also demonstrated that treatment with rosiglitazone significantly reduced both insulin and LPS levels in tandem. 4) It was also shown that LPS is significantly higher in NAFLD subjects, correlated with inflammatory cytokines and can be reduced by the use of Orlistat, an intestinal lipase inhibitor.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Endotoxins -- Analysis, Adipose tissues -- Research, Inflammation -- Immunological aspects, Cytokines -- Research
Date:	October 2009
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Kumar, Sudhesh ; McTernan, Philip
Extent:	217 leaves : ill., charts
Language:	eng
URI:	http://wrap.warwick.ac.uk/id/eprint/3134

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