title: Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis.
abstract: 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.
authors.affiliation: Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Takase
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Okazaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yagyu
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Okazaki
authors.forename: Takanari
authors.initials: T
authors.lastname: Gotoda
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000201:enzymology; D020738:Leptin / Q000172:deficiency; D008049:Lipase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology; D051379:Mice; D002787:Sterol Esterase / Q000172:deficiency / Q000378:metabolism*
chemical_list: D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D020738:Leptin; D002787:Sterol Esterase; D008049:Lipase