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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #319811
Title: Acylcarnitines: old actors auditioning for new roles in metabolic physiology

Author
item MCCOIN, COLLIN - University Of California
item KNOTTS, TRINA - University Of California
item Ferruzzi, Mario - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Nature Reviews Endocrinology
Publication Type: Review Article
Publication Acceptance Date: 7/23/2015
Publication Date: 8/25/2015
Citation: Mccoin, C.S., Knotts, T.A., Adams, S.H. 2015. Acylcarnitines: Old actors auditioning for new roles in metabolic physiology. Nature Reviews Endocrinology. doi:10.1038/2015.129.

Interpretive Summary: A number of challenges or perturbations in metabolic pathways lead to significant increases in plasma and tissue long-chain acylcarnitines (LCAC). The LCAC and other acylcarnitines rise, for instance, in the blood and muscle during exercise bouts, as tissue acyl-CoA pools change with accelerated metabolic fuel flux that is not perfectly coupled to mitochondrial energy demand and tricarboxylic acid cycle (TCA) capacity. This natural ebb and flow of acylcarnitine generation and accumulation may be contrasted with that observed under the more extreme conditions of inherited fatty acid oxidation disorders (FAOD), cardiac ischemia or Type 2 diabetes (T2D) that can lead to very high (FAOD, ischemia) or modestly increased (T2D) tissue and blood LCAC. Plasma LCAC profiles have long been used as diagnostic markers reflecting FAOD, but less research has been performed investigating the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as normal, physiological modulators of cell metabolism. A growing body of evidence has raised awareness of the possible impact of LCAC on cardiac ischemia phenotype, insulin resistance and inflammation. This comprehensive review covers the breadth of literature examining the potential consequences of LCAC build-up across a number of tissues and systems.

Technical Abstract: A number of challenges or perturbations in metabolic pathways lead to significant increases in plasma and tissue long-chain acylcarnitines (LCAC). The LCAC and other acylcarnitines rise, for instance, in the blood and muscle during exercise bouts, as tissue acyl-CoA pools change with accelerated metabolic fuel flux that is not perfectly coupled to mitochondrial energy demand and tricarboxylic acid cycle (TCA) capacity. This natural ebb and flow of acylcarnitine generation and accumulation may be contrasted with that observed under the more extreme conditions of inherited fatty acid oxidation disorders (FAOD), cardiac ischemia or Type 2 diabetes (T2D) that can lead to very high (FAOD, ischemia) or modestly increased (T2D) tissue and blood LCAC. Plasma LCAC profiles have long been used as diagnostic markers reflecting FAOD, but less research has been performed investigating the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as normal, physiological modulators of cell metabolism. A growing body of evidence has raised awareness of the possible impact of LCAC on cardiac ischemia phenotype, insulin resistance and inflammation. This comprehensive review covers the breadth of literature examining the potential consequences of LCAC build-up across a number of tissues and systems.