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Adipose tissue derived IL-6: Regulation of release and physiological significance.

Clarke, D.K.; (2004) Adipose tissue derived IL-6: Regulation of release and physiological significance. Doctoral thesis, University of London. Green open access

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Abstract

Signals derived from adipose tissue, such as interleukin-6 (IL-6), might explain the link between obesity and type 2 diabetes and cardiovascular disease. Significant amounts of IL-6 are released by adipose tissues. However, whether adipocytes within the tissue are responsible for the release, how this release is regulated and what the paracrine/autocrine effects of this adipokine might be are not known. Rodent obesity, as with human obesity, is associated with elevated plasma IL-6 concentrations. In both lean and obese animals, the epididymal fat depot released more IL-6 than did the subcutaneous, but was only significantly different in the obese [lean; 2.8 (2.5-5.9) pg/ml vs. obese; 8.6 (4.6-24.5) pg/ml, median (interquartile range), p=0.0001]. Furthermore, whereas subcutaneous adipose tissue from both lean and obese animals released comparable levels of IL-6, epididymal IL-6 production increased significantly in obesity. A large proportion (up to 50%) of adipose tissue IL-6 secretion, from both depots, was constitutive. However, following stimulation, the largest change in the rate of production of IL-6 was observed in the epididymal tissue of obese animals. Although both the basal and stimulated release was found to be through a Golgi-dependant process, this release was transcriptionally regulated and, unlike leptin, IL-6 was not stored within the adipocytes prior to release. The chronic exposure of differentiating preadipocytes to IL-6 enhanced lipid accumulation within the adipocytes. This lead to increased leptin secretion from the IL-6-treated cells, without an increase in ob expression. IL-6 did not affect the recruitment of preadipocytes to adipogenesis, nor did it increase the expression of the adipogenic modulators PPARy or C/EBP. However, in differentiated adipocytes, IL-6 treatment enhanced basal and insulin-stimulated glucose uptake and caused a reduction in adrenergically stimulated lipolysis. In conclusion, chronic hyper-secretion of IL-6 from adipocytes causes increased lipid deposition and adipocyte hypertrophy, indirectly inducing insulin resistance.

Type: Thesis (Doctoral)
Title: Adipose tissue derived IL-6: Regulation of release and physiological significance.
Identifier: PQ ETD:602608
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
UCL classification: UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
URI: http://discovery.ucl.ac.uk/id/eprint/1446683
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