Abstract 2230 A Role for Intestinal Stearoyl-CoA Desaturase in Modulating Acute Colonic Inflammation

Stearoyl-CoA desaturase (SCD) is a membrane-bound enzyme of the endoplasmic reticulum, responsible for the conversion of saturated fatty acids to monounsaturated fatty acids, via insertion of a double bond at the delta-9 position. Although extensively studied in tissues such as adipocytes, liver, and skin, little is known about the role of SCD in the intestines. In this study, we assessed the role of intestinal SCD in modulating colonic inflammation and health using a novel mouse model lacking intestinal desaturases SCD1 and SCD2 (dKO). Spontaneous appearance of rectal prolapse by 14 weeks of age was observed in dKO but not in wild type (WT) mice, on chow diet. This led us to test acute inflammatory responses in dKO, using a model of chemically induced colitis with dextran sulfate sodium (DSS). dKO and WT mice on a chow diet were treated with 3% DSS in drinking water for 5 days, before being euthanized. dKO mice showed earlier and more severe disease onset compared to WT mice, shown by early appearance of blood in the feces, and higher weight loss throughout DSS treatment. dKO mice had significantly larger spleen and shorter colons compared to treated WT mice. dKO mice had exacerbated colonic inflammatory response to DSS as established by increased colonic IL-6, IL-1b and LCN2, as well as significantly higher plasma LCN2 levels. These observations were confirmed by histological analysis of colonic tissues, showing more severe crypt erosion and immune cell infiltration in dKO than WT mice. The disease severity observed in dKO mice was reduced with the feeding of an oleic-supplemented diet, apparent as lower body weight loss and later appearance of fecal blood, as well as lower plasma LCN2 levels and lessened crypt erosions. Our results indicate that mice lacking intestinal SCD are more prone to chemically induced colitis, with improved disease outcome upon dietary supplementation of the SCD product, oleate. Overall, these outcomes suggest a role for intestinal stearoyl-CoA desaturase and its monounsaturated fatty acid product, in modulating acute colonic inflammatory responses with implications for clinical management of inflammatory bowel disease.