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. 2018 Dec 14;19(12):4058. doi: 10.3390/ijms19124058

Figure 2.

Figure 2

Interaction between lipids and innate immune receptors. Some lipid products, such as oxidized and modified LDL, cholesterol crystals, and ceramides activate innate immune receptors, such as TLR and NLRP3. FFA activate NLRP3, but not TLR. However, TLR-activation is a prerequisite for FFA to induce inflammation. HMBG1 (High Mobility Group Box 1) and fetuin A mediate TLR4 activation. Upon ligand binding, TLR trigger the activation JNK (c-Jun N-terminal kinase) and IKKβ (inhibitor of nuclear factor kappa-B kinase subunit β), leading to the induction of inflammatory gene transcription factors and the expression of proinflammatory cytokines, such as IL-1β and IL-8. NLRP3 activation leads to the expression of proinflammatory cytokines through the assembly of a large multiprotein complex, the inflammasome. The inflammasome consists of the NLRP3 protein, the adapter apoptosis-associated speck-like protein, and pro-caspase-1. The NLRP3-inflammasome catalyzes the cleavage, activation and secretion of IL-1β and IL-18. Inflammation promotes the development of steatosis in the liver, adipose lipolysis, peripheral insulin resistance, leptin resistance in the central nervous system, it impairs insulin secretion in the pancreas, and it promotes the development and progression of atherosclerosis, leading to obesity, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD).