Ces1/Es-x deficiency results in obesity, hyperlipidemia and impaired energy metabolism

QUIROGA, ARIEL DARIO; LEHNER, RICHARD

Halifax

Conferencia; Canadian Lipoprotein Conference; 2011

Increased lipogenesis and fat absorption contribute to obesity and associated metabolic disorders. Mouse carboxylesterase 1/esterase-x (Ces1/Es-x) plays a regulatory role in intestinal and hepatic triglyceride metabolism and lipoprotein secretion. Mice lacking Ces1/Es-x fed chow diet present with increased body weight, increased adiposity and enlarged adipocytes, hyperlipidemia and fatty liver despite the same level of caloric intake as wild-type mice due to augmented lipogenesis, increased apoB-containing lipoprotein secretion and delayed lipoprotein clearance. Lipidomic analyses showed that livers from Ces1/Es-x deficient mice accumulate polyunsaturated fatty acids in triacylglycerol, while Ces1/Es-x overexpression results in the reduction of these fatty acids from triacylglycerol. Supplementation of Ces1/Es-x-deficient mice with polyunsaturated fatty acids reversed the lipogenic phenotype. These results suggest that Ces1/Es-x is involved in partitioning of regulatory fatty acids, thereby playing an important role in modulating the expression of enzymes that control lipid biosynthesis and secretion. Our studies suggest that pharmacological intervention leading to increased Ces1/Es-x activity may become attractive for treatment of obesity, fatty liver and hyperlipidemia.