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Journal of Lipid Research, Vol. 42, 1018-1024, July 2001
Copyright © 2001 by Lipid Research, Inc.
A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis
Makoto Miyazakia,
Young-Cheul Kima, and
James M. Ntambia,b
a Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706
b Department of Nutritional Sciences, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706
Correspondence to:
James M. Ntambi, ntambi{at}biochem.wisc.edu (E-mail)
Stearoyl-CoA desaturase (SCD) catalyzes the de novo biosynthesis of oleate and palmitoleate, which are the major fatty acids found in triglycerides, cholesteryl esters, and phospholipids. A high carbohydrate (lipogenic) diet induces lipogenic gene expression by sterol regulatory element binding protein 1 (SREBP-1c)-mediated gene transcription, leading to an increase in the synthesis of triglycerides. The lipogenic diet fed to mice with a null mutation in the SCD1 gene (SCD-/-) fails to induce the synthesis of triglycerides in liver, despite the induction of expression of SREBP-1 and its target genes, fatty acid synthase and glycerol-3-phosphate acyltransferase. The lipogenic diet led to a decrease in the levels of triglyceride, but an increase in the level of cholesteryl esters of saturated fatty acids. Feeding a lipogenic diet supplemented with high levels of oleate to the SCD-/- mice resulted in incorporation of oleate in the liver of SCD-/- mice, but failed to restore triglycerides to the levels in the normal mouse. Triglyceride synthesis, as measured by the incorporation of [3H]glycerol, was dramatically reduced in the liver of SCD-/- mouse fed a lipogenic diet compared with the normal mouse.
These observations demonstrate that induction of triglyceride synthesis is highly dependent on SCD1 gene expression. Miyazaki, M., Y-C. Kim, and J. M. Ntambi. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J. Lipid Res. 2001. 42: 1018;1024.
Supplementary key words:
triglycerides, cholesteryl esters, gene expression, SREBP

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|
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|
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|

|
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|
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 |
|

|
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|
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|
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|

|
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|
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|
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|
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|
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|
 |

|
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[Full Text]
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|
 |
|

|
 |

|
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Triglyceride accumulation protects against fatty acid-induced lipotoxicity
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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1899 - 1907.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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99(17):
11482 - 11486.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Lin, G. Schonfeld, P. Yue, and Z. Chen
Hepatic Fatty Acid Synthesis Is Suppressed in Mice With Fatty Livers Due to Targeted Apolipoprotein B38.9 Mutation
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2002;
22(3):
476 - 482.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow
Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice
PNAS,
October 16, 2001;
(2001)
231490498.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Miyazaki, H.-J. Kim, W. C. Man, and J. M. Ntambi
Oleoyl-CoA Is the Major de Novo Product of Stearoyl-CoA Desaturase 1 Gene Isoform and Substrate for the Biosynthesis of the Harderian Gland 1-Alkyl-2,3-diacylglycerol
J. Biol. Chem.,
October 12, 2001;
276(42):
39455 - 39461.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow
Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice
PNAS,
November 6, 2001;
98(23):
13294 - 13299.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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