Fig. 2

Activation of chronic inflammation in the adipose tissue. Several hypotheses suggest possible mechanisms for the activation of adipose tissue inflammation. Hypothesis (a) proposes that an increased nutrient intake leads to an accumulation of misfolded/unfolded proteins, which activates the UPR, activating inflammation. Hypothesis (b) postulates that overloading of adipocytes triggers infiltration of macrophages due to hypoxia, followed by activation of cytotoxic T cells, which subsequently initiate inflammatory cascades. Hypoxia results in necrosis, which further promotes macrophage infiltration (see c). Overloaded adipocytes and consequent mechanical stress can also directly activate immune pathogen sensors (d). Lastly, free fatty acids can promote inflammation via indirectly binding to TLRs, which activates JKN1. This in turn stimulates the secretion of chemokines, such as MCP1 (e). AGEs are also postulated to contribute to inflammation in the adipose tissue (f)