Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E

Kenta Magoori, Man Jong Kang, Mitsuko R. Ito, Hajime Kakuuchi, Ryoichi X. Ioka, Akihisa Kamataki, Dong Ho Kim, Hiroshi Asaba, Satoshi Iwasaki, Yumiko A. Takei, Masako Sasaki, Shinichi Usui, Mitsuyo Okazaki, Sadao Takahashi, Masao Ono, Masato Nose, Juro Sakai, Takahiro Fujino, Tokuo T. Yamamoto

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

LDL receptor-related protein 5 (LRP5) plays multiple roles, including embryonic development and bone accrual development. Recently, we demonstrated that LRP5 is also required for normal cholesterol metabolism and glucose-induced insulin secretion. To further define the role of LRP5 in the lipoprotein metabolism, we compared plasma lipoproteins in mice lacking LRP5, apolipoprotein E (apoE), or both (apoE;LRP5 double knockout). On a normal chow diet, the apoE;LRP5 double knockout mice (older than 4 months of age) had ∼60% higher plasma cholesterol levels compared with the age-matched apoE knockout mice. In contrast, LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. High performance liquid chromatography analysis of plasma lipoproteins revealed that cholesterol levels in the very low density lipoprotein and low density lipoprotein fractions were markedly increased in the apoE;LRP5 double knockout mice. There were no apparent differences in the pattern of apoproteins between the apoE knockout mice and the apoE; LRP5 double knockout mice. The plasma clearance of intragastrically loaded triglyceride was markedly impaired by LRP5 deficiency. The atherosclerotic lesions of the apoE;LRP5 double knockout mice aged 6 months were ∼3-fold greater than those in the age-matched apoE-knockout mice. Furthermore, histological examination revealed highly advanced arthrosclerosis, with remarkable accumulation of foam cells and destruction of the internal elastic lamina in the apoE;LRP5 double knockout mice. These data suggest that LRP5 mediates both apoe-dependent and apoE-independent catabolism of plasma lipoproteins.

Original languageEnglish
Pages (from-to)11331-11336
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number13
DOIs
Publication statusPublished - Mar 28 2003
Externally publishedYes

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-5
Low Density Lipoprotein Receptor-Related Protein-1
Apolipoproteins E
Hypercholesterolemia
Atherosclerosis
Fats
Knockout Mice
Plasmas
Lipoproteins
Cholesterol
Metabolism
Foam Cells
Apoproteins
VLDL Lipoproteins
Bone Development

ASJC Scopus subject areas

  • Biochemistry

Cite this

Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. / Magoori, Kenta; Kang, Man Jong; Ito, Mitsuko R.; Kakuuchi, Hajime; Ioka, Ryoichi X.; Kamataki, Akihisa; Kim, Dong Ho; Asaba, Hiroshi; Iwasaki, Satoshi; Takei, Yumiko A.; Sasaki, Masako; Usui, Shinichi; Okazaki, Mitsuyo; Takahashi, Sadao; Ono, Masao; Nose, Masato; Sakai, Juro; Fujino, Takahiro; Yamamoto, Tokuo T.

In: Journal of Biological Chemistry, Vol. 278, No. 13, 28.03.2003, p. 11331-11336.

Research output: Contribution to journalArticle

Magoori, K, Kang, MJ, Ito, MR, Kakuuchi, H, Ioka, RX, Kamataki, A, Kim, DH, Asaba, H, Iwasaki, S, Takei, YA, Sasaki, M, Usui, S, Okazaki, M, Takahashi, S, Ono, M, Nose, M, Sakai, J, Fujino, T & Yamamoto, TT 2003, 'Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E', Journal of Biological Chemistry, vol. 278, no. 13, pp. 11331-11336. https://doi.org/10.1074/jbc.M211987200
Magoori, Kenta ; Kang, Man Jong ; Ito, Mitsuko R. ; Kakuuchi, Hajime ; Ioka, Ryoichi X. ; Kamataki, Akihisa ; Kim, Dong Ho ; Asaba, Hiroshi ; Iwasaki, Satoshi ; Takei, Yumiko A. ; Sasaki, Masako ; Usui, Shinichi ; Okazaki, Mitsuyo ; Takahashi, Sadao ; Ono, Masao ; Nose, Masato ; Sakai, Juro ; Fujino, Takahiro ; Yamamoto, Tokuo T. / Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 13. pp. 11331-11336.
@article{e792f8cd036346c593504e4086fe4637,
title = "Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E",
abstract = "LDL receptor-related protein 5 (LRP5) plays multiple roles, including embryonic development and bone accrual development. Recently, we demonstrated that LRP5 is also required for normal cholesterol metabolism and glucose-induced insulin secretion. To further define the role of LRP5 in the lipoprotein metabolism, we compared plasma lipoproteins in mice lacking LRP5, apolipoprotein E (apoE), or both (apoE;LRP5 double knockout). On a normal chow diet, the apoE;LRP5 double knockout mice (older than 4 months of age) had ∼60{\%} higher plasma cholesterol levels compared with the age-matched apoE knockout mice. In contrast, LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. High performance liquid chromatography analysis of plasma lipoproteins revealed that cholesterol levels in the very low density lipoprotein and low density lipoprotein fractions were markedly increased in the apoE;LRP5 double knockout mice. There were no apparent differences in the pattern of apoproteins between the apoE knockout mice and the apoE; LRP5 double knockout mice. The plasma clearance of intragastrically loaded triglyceride was markedly impaired by LRP5 deficiency. The atherosclerotic lesions of the apoE;LRP5 double knockout mice aged 6 months were ∼3-fold greater than those in the age-matched apoE-knockout mice. Furthermore, histological examination revealed highly advanced arthrosclerosis, with remarkable accumulation of foam cells and destruction of the internal elastic lamina in the apoE;LRP5 double knockout mice. These data suggest that LRP5 mediates both apoe-dependent and apoE-independent catabolism of plasma lipoproteins.",
author = "Kenta Magoori and Kang, {Man Jong} and Ito, {Mitsuko R.} and Hajime Kakuuchi and Ioka, {Ryoichi X.} and Akihisa Kamataki and Kim, {Dong Ho} and Hiroshi Asaba and Satoshi Iwasaki and Takei, {Yumiko A.} and Masako Sasaki and Shinichi Usui and Mitsuyo Okazaki and Sadao Takahashi and Masao Ono and Masato Nose and Juro Sakai and Takahiro Fujino and Yamamoto, {Tokuo T.}",
year = "2003",
month = "3",
day = "28",
doi = "10.1074/jbc.M211987200",
language = "English",
volume = "278",
pages = "11331--11336",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

TY - JOUR

T1 - Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E

AU - Magoori, Kenta

AU - Kang, Man Jong

AU - Ito, Mitsuko R.

AU - Kakuuchi, Hajime

AU - Ioka, Ryoichi X.

AU - Kamataki, Akihisa

AU - Kim, Dong Ho

AU - Asaba, Hiroshi

AU - Iwasaki, Satoshi

AU - Takei, Yumiko A.

AU - Sasaki, Masako

AU - Usui, Shinichi

AU - Okazaki, Mitsuyo

AU - Takahashi, Sadao

AU - Ono, Masao

AU - Nose, Masato

AU - Sakai, Juro

AU - Fujino, Takahiro

AU - Yamamoto, Tokuo T.

PY - 2003/3/28

Y1 - 2003/3/28

N2 - LDL receptor-related protein 5 (LRP5) plays multiple roles, including embryonic development and bone accrual development. Recently, we demonstrated that LRP5 is also required for normal cholesterol metabolism and glucose-induced insulin secretion. To further define the role of LRP5 in the lipoprotein metabolism, we compared plasma lipoproteins in mice lacking LRP5, apolipoprotein E (apoE), or both (apoE;LRP5 double knockout). On a normal chow diet, the apoE;LRP5 double knockout mice (older than 4 months of age) had ∼60% higher plasma cholesterol levels compared with the age-matched apoE knockout mice. In contrast, LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. High performance liquid chromatography analysis of plasma lipoproteins revealed that cholesterol levels in the very low density lipoprotein and low density lipoprotein fractions were markedly increased in the apoE;LRP5 double knockout mice. There were no apparent differences in the pattern of apoproteins between the apoE knockout mice and the apoE; LRP5 double knockout mice. The plasma clearance of intragastrically loaded triglyceride was markedly impaired by LRP5 deficiency. The atherosclerotic lesions of the apoE;LRP5 double knockout mice aged 6 months were ∼3-fold greater than those in the age-matched apoE-knockout mice. Furthermore, histological examination revealed highly advanced arthrosclerosis, with remarkable accumulation of foam cells and destruction of the internal elastic lamina in the apoE;LRP5 double knockout mice. These data suggest that LRP5 mediates both apoe-dependent and apoE-independent catabolism of plasma lipoproteins.

AB - LDL receptor-related protein 5 (LRP5) plays multiple roles, including embryonic development and bone accrual development. Recently, we demonstrated that LRP5 is also required for normal cholesterol metabolism and glucose-induced insulin secretion. To further define the role of LRP5 in the lipoprotein metabolism, we compared plasma lipoproteins in mice lacking LRP5, apolipoprotein E (apoE), or both (apoE;LRP5 double knockout). On a normal chow diet, the apoE;LRP5 double knockout mice (older than 4 months of age) had ∼60% higher plasma cholesterol levels compared with the age-matched apoE knockout mice. In contrast, LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. High performance liquid chromatography analysis of plasma lipoproteins revealed that cholesterol levels in the very low density lipoprotein and low density lipoprotein fractions were markedly increased in the apoE;LRP5 double knockout mice. There were no apparent differences in the pattern of apoproteins between the apoE knockout mice and the apoE; LRP5 double knockout mice. The plasma clearance of intragastrically loaded triglyceride was markedly impaired by LRP5 deficiency. The atherosclerotic lesions of the apoE;LRP5 double knockout mice aged 6 months were ∼3-fold greater than those in the age-matched apoE-knockout mice. Furthermore, histological examination revealed highly advanced arthrosclerosis, with remarkable accumulation of foam cells and destruction of the internal elastic lamina in the apoE;LRP5 double knockout mice. These data suggest that LRP5 mediates both apoe-dependent and apoE-independent catabolism of plasma lipoproteins.

UR - http://www.scopus.com/inward/record.url?scp=0038515322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038515322&partnerID=8YFLogxK

U2 - 10.1074/jbc.M211987200

DO - 10.1074/jbc.M211987200

M3 - Article

VL - 278

SP - 11331

EP - 11336

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -