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Fig. 1 | Lipids in Health and Disease

Fig. 1

From: A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease

Fig. 1

NAFLD related lipotoxicity, IR and inflammation. Legend 1: Lipotoxicity promotes inflammation and insulin resistance (IR). In turn, IR increases adipocyte lipolysis and exacerbates lipotoxicity. By binding with specific receptors, saturated fatty acids (SFAs) activate nuclear factor-kappa B (NF-κB). In IR, liver expression of NF-κB is extremely high. Receptor activator of NF-κB (RANKL) binds to its receptor (RANK) in liver and activates the NF-κB pathway. Activation of NF-κB kinase-β (IKK-β) promotes expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). TNF-α increases adipocyte lipolysis, strengthens phosphorylation of insulin receptor substrate-1(IRS-1) and reduces AMPK activity. IL-6 activates the c-Jun N-terminal kinase (JNK) pathway and suppresses IL-1 induced secretion of insulin. TNF-α and IL-6 promote development of IR and NAFLD. Defciency of IKK-β promotes expression of anti-inflammatory cytokines, such as adiponectin. Adiponectin receptor 1 (AdipoR1) activates AMPK activity, which then suppresses DNL, increases fatty acid oxidation and promotes mitochondrial function. AdipoR2 activates peroxisome proliferator-activated receptor-alpha (PPAR-α) signaling, which exerts anti-inflammatory effects by regulating NF-κB. Adiponectin inhibits the development of IR and NAFLD

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