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Journal of Lipid Research, Vol. 50, S138-S143, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Metabolism

Fatty acid metabolism: target for metabolic syndrome

Salih J. Wakil¹ and Lutfi A. Abu-Elheiga

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030

This work is supported by grants from the National Institute of Health (GM-63115), the Hefni Technical Training Foundation, and the Medallion Foundation.

Published, JLR Papers in Press, December 1, 2008.

¹ To whom correspondence should be addressed. e-mail: swakil{at}bcm.edu

ABSTRACT

Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They are presently considered as an attractive target to regulate the human diseases of obesity, diabetes, cancer, and cardiovascular complications. In this review we discuss the role of fatty acid metabolism and its key players, ACC1 and ACC2, in animal evolution and physiology, as related to health and disease.

Supplementary key words acetyl-coenzyme A carboxylases 1 and 2 • ACC1 and ACC2 • fatty acid synthase • FAS • carnitine/palmitoyl-transferase 1 • CPT1 • acyl-CoA • AMP-activated kinase • AMPK

Abbreviations: ACC1, acetyl-coenzyme A carboxylase 1; ACC2, acetyl-coenzyme A carboxylase 2; acetyl-CoA, acetyl-coenzyme A; ACLY, ATP citrate lyase; AMPK, AMP-activated kinase; CAT, carnitine/acetyl-CoA; ChREBP, carbohydrate-responsive element-binding protein; CPT1, carnitine/palmitoyl-transferase 1; FA, fatty acid(s); FAS, fatty acid synthase; FASKOL, FAS knockout in liver; IRS, insulin receptor substrates; MCD, malonyl-CoA decarboxylase; SREBP, sterol response-elements binding protein; TG, triglyceride(s); WT, wild-type

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