Lipid-Induced Mechanisms of Metabolic Syndrome

Figure 3

FFA-induced insulin resistance through endoplasmic reticulum stress and oxidative stress. A high level of FFA induces an increase in the production of ROS by mitochondria and the formation of oxidative stress. ROS stimulates NF-κB, which promotes the synthesis of L-1β, IL-6, and TNF-α. These inflammatory cytokines contribute to obesity-associated local inflammation and directly induce insulin resistance. In response to the enhanced level of FFAs and other nutrients in fats, adipose cells can develop signs of ER stress. A decrease in SERCA expression promotes the development of ER stress. UPR triggers the activation of IRE. Activation of IRE induces interaction with TRAF protein, which stimulations activation of IKKβ and JNK kinases. Its reaction can phosphorylate the IRS, thus blocking insulin signaling. JNK and IKKβ also lead to NF-κB activation and the development of inflammation.