Figure 1.

O₂ and its regulation at the intestinal epithelial barrier site. (A) Counter current blood flow reduces local pO₂ along the crypt–villus axis and results in low pO₂ at the villus tip. (B) Histological section of small intestine; villus–crypt axis, BALB/cOlaHsd mouse. (C) Hypoxic/normoxic environment along crypt–villus axis. (C.1) Hypoxic condition or intermittent hypoxia at the upper part of the villa; inactive HIF hydroxylases. HIF-1 is composed of two subunits—oxygen-sensitive HIF-1α and HIF-1β. Due to low O₂, PHD activity is decreased. HIF-1α is stabilised and binds to ARNT in the presence of co-activator p300; altogether, it activates transcription factor of HIF target genes. (C.2) Normoxic conditions at the bottom of the crypt. In the presence of O₂, PHD enzyme hydroxylates the two proline residues on HIF, enabling the binding of VHL to the HIF subunit, which degrades HIF-1α subunits under normoxic conditions. Fatty acid oxidation (FAO) is predominately present in normoxic cells.