Deficiency of Carboxylesterase 1/Esterase-x in Mice Results in Obesity, Hepatic Steatosis and Hyperlipidemia

QUIROGA, ARIEL DARIO; LI, LENA; TRöTZMüLLER, MARTIN; NELSON, RANDY; PROCTOR, SPENCER D. ; KöFELER, HARARLD; LEHNER, RICHARD

HEPATOLOGY

Wiley

Año: 2012 vol. 1 p. 1 - 10

0171-6123

Increased lipogenesis, together with hyperlipidemia and increased fat deposition contribute to obesity and associated metabolic disorders including non-alcoholic fatty liver disease. Here we show that mouse carboxylesterase 1/esterase-x (Ces1/Es-x) plays a regulatory role in hepatic fat metabolism. We demonstrate that Ces1/Es-x knockout mice present with increased hepatic lipogenesis and with over secretion of apoB-containing lipoproteins (hepatic very-low density lipoproteins), which leads to hyperlipidemia and increased fat deposition in peripheral tissues. Consequently, Ces1/Es-x knockout mice develop obesity, fatty liver, hyperinsulinemia and insulin insensitivity on chow diet without change in food intake and present with decreased energy expenditure. Ces1/Es-x deficiency prevents the release of polyunsaturated fatty acids from triacylglycerol stores, leading to an up-regulation of SREBP1c-mediated lipogenesis, which can be reversed with dietary ù-3 fatty acids. Conclusion: These studies support a role for Ces1/Es-x in the partitioning of regulatory fatty acids and concomitant control of hepatic lipid biosynthesis, secretion and deposition.