Fig. 4.
Hypothetical model showing the molecular mechanism of AMPK-induced reduction in proinflammatory cytokines. Orexigenic metabolic factors, such as ghrelin, up-regulated during negative energy balance, bind to their specific receptors on immune cells and signal to inhibit NF-κB-mediated inflammation. The phosphorylation of IκB and subsequent translocation of p50 and p65 subunits to the nucleus and NF-κB activation are ATP-dependent events. An increase in intracellular AMP levels during this reaction may lead to activation of AMPK, which may directly block the NF-κB-mediated transcription of proinflammatory cytokines. GHS-R, Growth hormone secretatogue receptor.