Adipose Tissue as an Inflammatory Organ (Endocrine Tumor) in Human Obesity

- July 4, 2008

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Presentation

"Adipose Tissue as an Inflammatory Organ (Endocrine Tumor) in Human Obesity"

Prof. John N. Fain (biography)
English - 2005-06-10 - 55 minutes

(28 slides)

Summary :
We postulate that many of the deleterious effects of obesity in humans may involve enhanced formation of cytokines by the non-fat cells in adipose tissue. Cytokines are factors that are involved in the response to infections but also appear to promote heart disease as well as diabetes. We compared the release of cytokines by the adipose tissue of morbidly obese women with a body fat weight of 123 pounds and similar women one year after bariatric surgery when the body fat weight drops to 70 pounds. The major effect of the loss of weight was to reduce the secretion of tumor necrosis factor alpha [TNF alpha] and interleukin 8 [IL-8} by adipose tissue. TNF alpha is a cytokine originally postulated to kill cancer cells. However, it is now thought to be involved in blocking the effects of insulin. Type 2 diabetes is much more prevalent in women with a total body fat of 123 pounds as compared to those with a body fat weight of 70 pounds. Both IL-8 and TNF alpha are local hormones that do not ordinarily circulate in the blood but rather act on cells close to their sites of release. IL-8 is a chemokine that may recruit circulating blood cells into adipose tissue and there monocytes can turn into macrophages that are useful in fighting infection but also promote cardiovascular disease.

The current paradigm based on studies with murine adipocyte-like cells in culture is that the release of cytokines by adipose tissue is due to the adipocytes. However, our data indicate, that with the exception of leptin, the formation of adipokines/cytokines in human adipose tissue is primarily due to cells other than adipocytes. Some think that the major source of the cytokines is macrophages. We believe that cytokines may also be coming from mast cells as well as the endothelial cells of blood vessels in adipose tissue.

One problem we have in ex vivo studies with human adipose tissues is that many cytokines are upregulated after removal of adipose tissue. We are unsure what is responsible for the upregulation of COX-2 mRNA seen within 3 h but it occurs to the same extent when one cut piece of tissue is incubated in vitro as compared to minced pieces of adipose tissue. Cutting off the blood supply to the adipose tissue probably initiates a stress response. Both the temperature at which the fat is maintained prior to the start of the experiments and the composition of the buffer influence the upregulation of COX-2 based on PGE2 release.

Our current studies are designed to investigate the mechanisms involved in the upregulation of cytokine mRNA after removal of human adipose tissue and identification of the cells in human visceral adipose tissue responsible for formation of cytokines.

Learning objectives :
After viewing this presentation the participant will be able to discuss:

- The specific parts of adipose tissue that inflammatory factors come from

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