Fig. 6.

Proposed regulatory model of intestinal inflammation dependent on elevated LDs mediated by a negative FOXO3 and PGE2 regulatory loop. TNF receptor signaling leading to PI3K-mediated loss of FOXO3 appears to be the initial step that stimulates lipogenesis, initiates LD growth, and PGE2 synthesis. Increased lipogenesis and PGE2 synthesis further maintain the loss of FOXO3 function. When there are low cellular needs for lipids from LDs, lipogenesis and PGE2 synthesis would be attenuated, and FOXO3 activity recovered, supporting the existence of a negative LD-FOXO3-PGE2 regulatory loop. TNF-stimulated lipogenesis leads to elevated LDs and facilitates NF-κB-mediated IL-8, which is associated with the surface of LDs found in the ER and Golgi.