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Title: Signals from adipose tissue in morbid obesity and effect on depot specific differences
Author: Madani, R.
ISNI:       0000 0004 2733 0309
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2009
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Signals from adipose tissue, such as interleukin-6 (IL-6) and asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide inhibitor, explain the link between obesity and metabolic diseases. Previously published human studies have used omental adipose tissue to study visceral depots, based on the assumption that all visceral adipose tissues are similar. This study, for the first time, assessed the release of five adipokines (adiponectin, leptin, IL-6, MCP-1 and RANTES) from the subcutaneous and two omental depots. Components of the cyclooxygenase (COX) and the nitric oxide (NO) pathways, that regulate cytokine release in other tissues, were also investigated for their putative role(s) in mediating adipokine release. RANTES release was greatest from the gastric fat pad. However, significantly higher circulating RANTES levels suggest that adipose tissue is unlikely to be the main source of RANTES release. Inhibition of the COX pathway, especially COX-2, reduced IL-6 release from subcutaneous adipose tissue. Prostacyclin synthase (PGI2S) activity was higher in the omental tissue and its protein expression was elevated in the stromavascular fraction from this depot. PGI2S activity appears to mainly reside in the non-adipocyte cells and is more coupled to IL-6 production in adipose tissue. Serum insulin and CRP levels, and systolic blood pressure, directly associated with subcutaneous tissue ADMA content, while BMI correlated with omental ADMA release. ADMA release was higher from the omental depot. However, while DDAH2 expression was higher compared to DDAH1 in adipose tissue, there was no depot specific difference in the expression of either isoform. In conclusion, this study showed adipose depot specific differences of RANTES release, a novel adipokine, from a hitherto poorly studied depot, the gastric fat pad. Characteristics of the omental adipose tissues differed depending on location and paracrine factors that may mediate the adipokine release. These regulatory pathways included components of the COX and NO pathways.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available