Fig. 4
From: Relevance and consequence of chronic inflammation for obesity development
Pro-inflammatory cytokine SOCS3 has been proposed to play an important role in the development of leptin and insulin resistance in the CNS and the periphery. SOCS3 is activated and produced by DIO, injection of TNFα, or due to lipid infusion in several different organs. It is also activated upon increased levels of insulin and leptin and acts as a negative regulator for both, i.e., by inhibiting phosphorylation and p85 binding to insulin receptor substrate 1 (IRS-1), inhibiting insulin-stimulated glucose uptake or reducing the binding of leptin to the leptin-receptor in the hypothalamus, leading to orexigenic signaling. Chronic inflammation increases levels of IL-6, which in turn activates SOCS3 in the adipose tissue