Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis

Motohiro Sekiya, Jun-Ichi Osuga, Naoya Yahagi, Hiroaki Okazaki, Yoshiaki Tamura, Masaki Igarashi, Satoru Takase, Kenji Harada, Sachiko Okazaki, Yoko Iizuka, Ken Ohashi, Hiroaki Yagyu, Mitsuyo Okazaki, Takanari Gotoda, Ryozo Nagai, Takashi Kadowaki, Hitoshi Shimano, Nobuhiro Yamada, Shun Ishibashi
Journal of Lipid Research 2008, 49 (8): 1829-38
Hormone-sensitive lipase (HSL) regulates the hydrolysis of acylglycerol and cholesteryl ester (CE) in various 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 lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) showed massive accumulation of CE in the liver compared with Lep(ob/ob)/HSL(+/+) mice, while triacylglycerol (TG) accumulation was modest. Similarly, feeding with a high-cholesterol diet induced hepatic CE accumulation in HSL(-/-) mice. Supporting these observations, we detected significant expression of protein as well as mRNA of HSL in the liver. HSL(-/-) mice showed reduced activity of CE hydrolase, but not of TG lipase, 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(-/-) mice showed reduced activity of CE hydrolase and contained more CE than those from HSL(+/+) mice even without 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 involved in the hydrolysis of CE in hepatocyes.

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