Abstract 1186: Overexpression Of Endothelial Lipase In The Liver Promotes The Clearance Of Plasma Lipids But Accelerates Liver Steatosis In A Mouse Model Of Metabolic Syndrome
The metabolic syndrome includes high triglyceride (TG) and low HDL-cholesterol (HDL-C) levels in the plasma, and often accompanies steatosis in the liver. Endothelial lipase (EL) is a phospholipase that regulates HDL metabolism. EL is expressed by hepatocytes, while the function of EL in the liver has not been identified. Here, we examined the role of EL in the liver using a mouse model of metabolic syndrome. The EL expression in the liver was analyzed by real-time PCR. It revealed that liver EL expression was significantly increased in obese and diabetic db/db mice compared to that of control mice. To examine the significance of the EL upregulation in the liver, we injected the recombinant adenovirus encoding human EL into mice. The EL overexpression in the liver resulted in a significant decrease in plasma HDL-C, TG, and free fatty acid levels. Interestingly, the EL overexpression in the liver increased liver weight and liver TG content both in wild-type and db/db mice. In db/db mice, particularly, EL overexression accelerated the formation of steatosis by increasing the mRNA level of fatty acid synthase. These findings indicate that EL expression is increased in the liver in the metabolic syndrome. The upregulation of EL promotes the uptake of plasma lipids by hepatocytes, and accelerates the progression of steatosis in db/db mice. Thus EL may play a role in the genesis of steatosis as well as dyslipidemia in the metabolic syndrome.