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Nat Rev Endocrinol. 2015 Oct;11(10):617-25. doi: 10.1038/nrendo.2015.129. Epub 2015 Aug 25.

Acylcarnitines--old actors auditioning for new roles in metabolic physiology.

Author information

1
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
2
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, USA.
3
Arkansas Children's Nutrition Center and Department of Pediatrics, University of Arkansas for Medical Sciences, 15 Children's Way, Little Rock, AR 72202, USA.

Abstract

Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma concentrations of LCACs and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

PMID:
26303601
PMCID:
PMC4966159
DOI:
10.1038/nrendo.2015.129
[Indexed for MEDLINE]
Free PMC Article

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