carboxylesterase1esterase-x regulates chylomicron production in mice在老鼠carboxylesterase1esterase-x调节乳糜微粒生产.pdfVIP

Carboxylesterase1/Esterase-x Regulates Chylomicron Production in Mice Ariel D. Quiroga1,2, Jihong Lian1,2, Richard Lehner1,2,3* 1 Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada, 2 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada, 3 Department of Cell Biology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Abstract Elevated postprandial plasma triacylglycerol (TG) concentrations are commonly associated with obesity and the risk of cardiovascular disease. Dietary fat contributes to this condition through the production of chylomicrons. Carboxylesterases have been mainly studied for their role in drug metabolism, but recently they have been shown to participate in lipid metabolism; however, their role in intestinal lipid metabolism is unknown. Carboxylesterase1/esterase-x (Ces1/Es-x) deficient mice become obese, hyperlipidemic and develop hepatic steatosis even on standard chow diet. Here, we aimed to explore the role of Ces1/Es-x in intestinal lipid metabolism. Six-month old wild-type and Ces1/Es-x deficient mice were maintained on chow diet and intestinal lipid metabolism and plasma chylomicron clearance were analyzed. Along the intestine Ces1/Es-x protein is expressed only in proximal jejunum. Ablation of Ces1/Es-x expression results in postprandial hyperlipidemia due to increased secretion of chylomicrons. The secreted chylomicrons have aberrant protein composition, which results in their reduced clearance. In conclusion, Ces1/Es-x participates in the regulation of chylomicron assembly and secretion. Ces1/Es-x might act as a lipid sensor in enterocytes regulating chylomicron secretion rate. Ces1/Es-x might represent an attractive pharmacological target