SPHINGOLIPID METABOLISM AND ITS EFFECT ON INTESTINAL HEALTH IN RELATION TO INFLAMMATORY BOWEL DISEASE

Abstract

Inflammatory bowel disease has been linked with the endoplasmic reticulum stress (ER stress) in response to saturated fatty acids (SFAs). Patients with IBD also have a higher chance of colorectal cancer (CRC). SFA myristate (C:14) and the corresponding ceramide synthases, Cers5 and Cers6, initiate inflammatory pathways within the intestine. To determine the effect of SFAs on IBD, ER stress, and downstream signals of inflammation, we treated colon cells with Cers5, Cers6, and Cers 5 & 6 knockouts with myristate. Once treated, downstream inflammatory signals, such as the protein XBP1 were observed to see if the treatment affected splicing, which would continue the downstream inflammatory signaling, which leads to apoptosis of the inflamed cells. The same pattern can be seen when colon cancer cells are treated with myristate. We can conclude that XBP1 splicing increases when treated with myristate in the healthy intestinal cells and the colon cancer cells. This suggests that myristate plays a larger role in ER stress and intestinal inflammation correlated with IBD and CRC.