Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis

Hormone-sensitive lipase (HSL) regulates the hydrolysis of acylglycerol and cholesteryl ester (CE) in var- ious organs, including adipose tissues. However, the hepatic expression level of HSL has been reported to be almost negligible. In the present study, we found that mice lack- ing both leptin and HSL (Lep ob/ob /HSL 2/2 ) showed mas- sive accumulation of CE in the liver compared with Lep ob/ob / HSL 1/1 mice, while triacylglycerol (TG) accumulation was modest. Similarly, feeding with a high-cholesterol diet in- duced hepatic CE accumulation in HSL 2/2 mice. Supporting these observations, we detected significant expression of pro- tein as well as mRNA of HSL in the liver. HSL 2/2 mice showed reduced activity of CE hydrolase, but not of TG li- pase, in the liver compared with wild-type mice. Furthermore, we confirmed the expression of HSL in viable parenchymal cells isolated from wild-type mice. The hepatocytes from HSL 2/2 mice showed reduced activity of CE hydrolase and containedmoreCEthanthosefromHSL 1/1 miceevenwithout the incubation with lipoproteins. Incubation with LDL further augmented the accumulation of CE in the HSL-deficient hepatocytes. From these results, we conclude that HSL is in- volved in the hydrolysis of CE in hepatocyes.—Sekiya, M., J-i. Osuga, N. Yahagi, H. Okazaki, Y. Tamura, M. Igarashi, S. Takase, K. Harada, S. Okazaki, Y. Iizuka, K. Ohashi, H. Yagyu, M. Okazaki, T. Gotoda, R. Nagai, T. Kadowaki, H. Shimano, N. Yamada, and S. Ishibashi. Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis. J. Lipid Res. 2008. 49: 1829-1838.