Spatio‐Nutritional Regulation of Intestinal Desaturases

Abstract

Stearoyl‐CoA desaturases are ER‐resident enzymes that convert saturated fatty acids into monounsaturated fatty acids and have been studied using whole body, liver, skin, and adipose knockout models, but their specific role in the intestine is not well understood. Stearoyl‐CoA desaturase 1 (SCD1) gene and protein expression increases along the length of the intestine and was found to be induced by fasting followed by refeeding a high sucrose very low‐fat diet, similar to what has been established in liver. In addition to SCD1, stearoyl‐CoA desaturase 2 (SCD2) was also found to be expressed and regulated in a similar manner to SCD1 in the intestine. Intestine specific SCD1 knockout (iKO) mice were generated by crossing SCD1 floxed mice with mice expressing the Cre‐recombinase gene under the villin promoter. These mice have longer intestines and increased lipid absorption compared to floxed counterparts. In addition, iKO mice have increased bile acids, a more hydrophilic bile acid pool, and have increased plasma GLP‐1 and brown adipose tissue (BAT) Iodothyronine Deiodinase 2 (Dio2) gene expression. When placed on a low‐fat diet (10% fat) or a high‐fat diet (45% fat), the iKO mice had increased food intake and energy expenditure while maintaining similar or leaner body weights as their floxed counterparts. The iKO mice showed a trend of improved glucose tolerance. Overall, these results show that stearoyl‐CoA desaturases are expressed and regulated in the intestine. Knocking out SCD1 in an intestine‐specific manner leads to increased bile acids and these increased bile acids may contribute to the increased GLP‐1 and bile acid‐induced thermogenesis in BAT. When fed a high fat diet, iKO mice demonstrated an increased basal metabolic rate, increased food intake, and improved glucose tolerance.