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 for the treatment of
lipid abnormalities associated with
obesity,
insulin resistance and
fatty liver disease.