Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement.
We have previously demonstrated that neutral cholesterol ester hydrolase 1 (Nceh1) regulates foam cell formation and atherogenesis through the catalytic activity of cholesterol ester hydrolysis, and that Nceh1 and hormone-sensitive lipase (Lipe) are responsible for the majority of neutral cholesterol ester hydrolase activity in macrophages. There are several cholesterol ester-metabolizing tissues and cells other than macrophages, among which adrenocortical cells are also known to utilize the intracellular cholesterol for steroidogenesis. It has been believed that the mobilization of intracellular cholesterol ester in adrenal glands was facilitated solely by Lipe. We herein demonstrate that Nceh1 is also involved in cholesterol ester hydrolysis in adrenal glands. While Lipe deficiency remarkably reduced the neutral cholesterol ester hydrolase activity in adrenal glands as previously reported, additional inactivation of Nceh1 gene completely abrogated the activity. Adrenal glands were enlarged in proportion to the degree of reduced neutral cholesterol ester hydrolase activity, and the enlargement of adrenal glands and the accumulation of cholesterol esters were most pronounced in the Nceh1/Lipe double-deficient mice. Thus Nceh1 is involved in the adrenal cholesterol metabolism, and the cholesterol ester hydrolytic activity in adrenal glands is associated with the organ enlargement.
The Department of Metabolic Diseases, University of Tokyo, Tokyo 113-8655, Japan.
Keisuke
K
Ohta
Motohiro
M
Sekiya
Hiroshi
H
Uozaki
Masaki
M
Igarashi
Satoru
S
Takase
Masayoshi
M
Kumagai
Mikio
M
Takanashi
Yoshinori
Y
Takeuchi
Yoshihiko
Y
Izumida
Midori
M
Kubota
Makiko
M
Nishi
Hiroaki
H
Okazaki
Yoko
Y
Iizuka
Naoya
N
Yahagi
Hiroaki
H
Yagyu
Masashi
M
Fukayama
Takashi
T
Kadowaki
Ken
K
Ohashi
Shun
S
Ishibashi
Jun-ichi
J
Osuga
D000311:Adrenal Glands / Q000033:anatomy & histology* / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000172:deficiency*; D015870:Gene Expression; D006868:Hydrolysis; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000187:drug effects; D057057:Serine Proteases / Q000235:genetics*; D002787:Sterol Esterase / Q000235:genetics*
D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; C514712:Nceh1 protein, mouse; D002787:Sterol Esterase; D057057:Serine Proteases