Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis
| Autor: | Jianqiang Mao, Salih J. Wakil, Parichher Kordari, Subrahmanyam S. Chirala, Huiguang Li, Tattym Shaikenov, Francesco J. DeMayo, Zi-Wei Gu, Lutfi Abu-Elheiga, William C. Heird |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Carbohydrate metabolism Mice chemistry.chemical_compound Internal medicine medicine Animals Homeostasis Glucose homeostasis Obesity Beta oxidation Triglycerides Fatty acid synthesis Mice Knockout Multidisciplinary biology Triglyceride Acetyl-CoA carboxylase Biological Sciences Lipid Metabolism Animal Feed Dietary Fats Rats Up-Regulation Malonyl Coenzyme A Mice Inbred C57BL Fatty acid synthase Glucose Endocrinology Gene Expression Regulation Liver chemistry Biochemistry Ketone bodies biology.protein Gene Deletion Acetyl-CoA Carboxylase |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:8552-8557 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0603115103 |
| Popis: | In animals, liver and white adipose are the main sites for the de novo fatty acid synthesis. Deletion of fatty acid synthase or acetyl-CoA carboxylase (ACC) 1 in mice resulted in embryonic lethality, indicating that the de novo fatty acid synthesis is essential for embryonic development. To understand the importance of de novo fatty acid synthesis and the role of ACC1-produced malonyl-CoA in adult mouse tissues, we generated liver-specific ACC1 knockout (LACC1KO) mice. LACC1KO mice have no obvious health problem under normal feeding conditions. Total ACC activity and malonyl-CoA levels were ≈70–75% lower in liver of LACC1KO mice compared with that of the WT mice. In addition, the livers of LACC1KO mice accumulated 40–70% less triglycerides. Unexpectedly, when fed fat-free diet for 10 days, there was significant up-regulation of PPARγ and several enzymes in the lipogenic pathway in the liver of LACC1KO mice compared with the WT mice. Despite the significant up-regulation of the lipogenic enzymes, including a >2-fold increase in fatty acid synthase mRNA, protein, and activity, there was significant decrease in the de novo fatty acid synthesis and triglyceride accumulation in the liver. However, there were no significant changes in blood glucose and fasting ketone body levels. Hence, reducing cytosolic malonyl-CoA and, therefore, the de novo fatty acid synthesis in the liver, does not affect fatty acid oxidation and glucose homeostasis under lipogenic conditions. |
| Databáze: | OpenAIRE |
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