Fig. 1.

Working mechanisms of IAP. High levels of ATP lead to intestinal dysbiosis. IAP can dephosphorylate ATP to other nucleotides and thus regulate the number and diversity of commensal bacteria. LPS causes TLR4 activation which further promotes the release of inflammatory mediators. LPS can transfer through the intercellular space or bind to chylomicrons which leads to more LPS absorption in the context of an HFD. Released inflammatory mediators and absorbed LPS can cause local intestinal inflammation and chronic systemic inflammation. IAP removes 1 of the 2 phosphate groups from LPS and reduces its toxicity; dephosphorylated LPS can still bind to TLR4 but mainly acts as a TLR antagonist, thus inhibiting downstream intracellular signaling. IAP also regulates the levels of intestinal intercellular tight junction proteins (TJP) and their cellular localization and reduces the translocation of LPS.