Deficiency in hepatic ATP-citrate lyase affects VLDL-triglyceride mobilization and liver fatty acid composition in mice.
J Lipid Res
; 51(9): 2516-26, 2010 Sep.
Article
in En
| MEDLINE
| ID: mdl-20488800
ABSTRACT
ATP-citrate lyase (ACL) is a key lipogenic enzyme that converts citrate in the cytoplasm to acetyl-CoA, the initial precursor that yields malonyl-CoA for fatty acid biosynthesis. As cytosolic citrate is derived from the tricarboxylic acid cycle in the mitochondrion, ACL catalyzes a critical reaction linking cellular glucose catabolism and lipid synthesis. To investigate the metabolic action of ACL in lipid homeostasis, we specifically knocked down hepatic ACL expression by adenovirus-mediated RNA interference in mice maintained on a low-fat or high-fat diet. Hepatic ACL abrogation markedly reduced the liver abundance of both acetyl-CoA and malonyl-CoA regardless of dietary fat intake, which was paralleled with decreases in circulating levels of triglycerides and free fatty acids. Moreover, hepatic ACL knockdown resulted in diet-dependent changes in the expression of other lipogenic enzymes, accompanied by altered fatty acid compositions in the liver. Interestingly, ACL deficiency led to reduced serum VLDL-triglyceride levels but increased hepatic triglyceride content, resulting at least partially from decreased hepatic secretion of VLDL-containing apolipoprotein B-48. Together, these results demonstrate that hepatic ACL suppression exerts profound effects on triglyceride mobilization as well as fatty acid compositions in the liver, suggesting an important role for ACL in lipid metabolism.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
ATP Citrate (pro-S)-Lyase
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Triglycerides
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Fatty Acids
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Lipoproteins, VLDL
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Liver
Limits:
Animals
Language:
En
Journal:
J Lipid Res
Year:
2010
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA