Energy-sensitive AMPK-SIRT1 pathway and the regulation of inflammation

AMP-activated protein kinase(AMPK) is a crucial kinase involved in the modulation of cellular energy metabolism, and it also has SIRT1-dependent anti-inflammatory activity. The mechanisms through which AMPK activate SIRT1 include promoting the generation of SIRT1 activator NAD+, relieving the suppressive effects on the activity of SIRT1 by DBC1 and on the expression of SIRT1 by p53. SIRT1 then modulates the inflammatory response through deacetylating nuclear factor kappa B(NF-κB), activator protein 1(AP-1) and histones, thus leading to suppressed transcriptional activities of transcription factors, altered conformation of chromatin, and eventually, transcriptional repression of inflammation-related genes. In addition, AMPK activator and the clinic antidiabetic metformin have protective benefits in various animal models with inflammation-related disorders through activating AMPK. Thus, AMPK-SIRT1 pathway might become a novel target for anti-inflammatory therapy.