Abstract 2399 SCD1 Upregulation Partially Compensates for loss of SCD2 in Mouse Intestine

Monounsaturated fatty acids (MUFAs) are preferred substrates for the synthesis of stored lipids and can be acquired from the diet or endogenously synthesized by desaturation of saturated fatty acids (SFAs). The stearoyl-CoA desaturase (SCD) enzymes insert a double bond at the D9 position of 12-18C SFAs, catalyzing their conversion to MUFAs. We have previously shown that mice lacking the SCD1 isoform in the intestine have reductions in intestinal and systemic lipids, along with alterations in whole body energy balance, bile acid levels, and glucose homeostasis. Mice express two isoforms of SCD in the intestine, SCD1 and SCD2, and the role of intestinal SCD2 is not known. Like SCD1, we discovered that Scd2 gene expression increases along the length of the gastrointestinal tract, but is ∼10-fold higher than that of Scd1. Similar to Scd1, expression of Scd2 is also upregulated along the length of the intestine by a fasting-refeeding regimen. To investigate the role of SCD2 in the intestine, we generated intestine-specific SCD2 knockout mice (2iKO). SCD2 deletion altered lipid content and composition in the gut, in circulation, and in the liver, although not to the same extent observed in mice lacking intestinal SCD1. Specifically, plasma and hepatic TG levels were reduced in 2iKO mice with variable reductions observed in the 16:1/16:0 and 18:1/18:0 desaturation ratios. Interestingly, the 14:1/14:0 desaturation ratio, which was significantly reduced in mice lacking intestinal SCD1, was significantly increased in many lipid fractions in the liver, plasma, and gut of 2iKO mice. In the colon of 2iKO mice, 16:1 and 18:1 ratios were also increased, along with the 14:1 desaturation ratio. These alterations were accompanied by significant increases in SCD1 expression in the colon of 2iKO mice. Despite these moderate changes in lipid content and composition, 2iKO mice did not display any alterations in energy homeostasis or glucose metabolism, even when challenged with a high-fat diet. Additionally, 2iKO mice did not display any differences in small intestine length, colon length, villus lengths and widths, or crypt depths. Taken together, these data suggest that deletion of intestinal SCD2 does not significantly impact systemic energy metabolism, potentially due to compensatory changes in SCD1 expression.