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BMC Proceedings

Volume 6 Supplement 3

Metabolism, diet and disease

Open Access

SIRT4 controls the balance between lipid synthesis and catabolism by repressing malonyl-CoA decarboxylase

  • Gaëlle Laurent1,
  • Natalie J German1,
  • Asish K Saha2,
  • Vincent CJ de Boer1, 3,
  • Frank Fischer4,
  • Gina Boanca4,
  • Noah Dephoure5,
  • Bhavapriya Vaitheesvaran6,
  • Michael Davies7,
  • Steven P Gygi5,
  • Deborah M Muoio7,
  • Irwin J Kurland6,
  • Clemens Steegborn4,
  • Neil B Ruderman2 and
  • Marcia C Haigis1
BMC Proceedings20126(Suppl 3):P30

https://doi.org/10.1186/1753-6561-6-S3-P30

Published: 1 June 2012

Lipid metabolism is highly controlled by the nutritional state of the organism. In this study, we identify the mitochondrial sirtuin, SIRT4, as a critical regulator of lipid homeostasis. We find that SIRT4 represses fatty acid oxidation while promoting lipid anabolism. Mechanistically, SIRT4 regulates this balance by inhibiting malonyl-CoA decarboxylase (MCD), an enzyme that produces acetyl-CoA from malonyl-CoA, a precursor for lipogenesis that also inhibits mitochondrial fat oxidation. We find that SIRT4 is active in nutrient-rich conditions, such as in the fed state. As a consequence, SIRT4 null mice display reduced levels of malonyl-CoA in skeletal muscle and white adipose tissue in the fed state and fail to further lower malonyl-CoA levels during fasting. SIRT4 null mice possess a catabolic signature of lipid metabolism and demonstrate decreased de novo lipogenesis. These studies highlight SIRT4 as a novel regulator of MCD activity and malonyl-CoA levels, providing new insight into the regulation of lipid homeostasis.

Authors’ Affiliations

(1)
Department of Cell Biology, The Paul F. Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School
(2)
Diabetes Research Unit, Section of Endocrinology, Department of Medicine, Boston University Medical Center
(3)
Laboratory Genetic Metabolic Diseases, Academic Medical Center
(4)
Department of Biochemistry, University of Bayreuth
(5)
Department of Cell Biology, Harvard University Medical School
(6)
Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine
(7)
Departments of Medicine and Pharmacology & Cancer Biology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center

Copyright

© Laurent et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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