Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis.
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.
Sekiya
Motohiro
M
Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Osuga
Jun-Ichi
J
Yahagi
Naoya
N
Okazaki
Hiroaki
H
Tamura
Yoshiaki
Y
Igarashi
Masaki
M
Takase
Satoru
S
Harada
Kenji
K
Okazaki
Sachiko
S
Iizuka
Yoko
Y
Ohashi
Ken
K
Yagyu
Hiroaki
H
Okazaki
Mitsuyo
M
Gotoda
Takanari
T
Nagai
Ryozo
R
Kadowaki
Takashi
T
Shimano
Hitoshi
H
Yamada
Nobuhiro
N
Ishibashi
Shun
S
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*
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D020738:Leptin; D002787:Sterol Esterase; D008049:Lipase