Role Of Proinflammatory Mediators

As described, aging is associated with increased levels of pro-inflammatory cytokines originating from the dysfunction of the immune system and from the altered adipose tissue distribution toward a central predominance. These cytokines are known to enhance adipocyte lipolysis, which further increases the FFA levels, which, as mentioned, exert a negative effect on insulin signaling. Thus exists a vicious cycle, as pro-inflammatory cytokines increase FFA levels, which through the activation of NFkB increases the pro-inflammatory cytokines. In rodent models the neutralization of TNF-a was shown to almost reverse insulin resistance. In humans their contribution is still strongly debated.

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