Madani, R. (2009) Signals from adipose tissue in morbid obesity and effect on depot specific differences. Doctoral thesis, UCL (University College London).
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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.
|Title:||Signals from adipose tissue in morbid obesity and effect on depot specific differences|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of General Surgery|
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics
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