IMR Press / FBL / Volume 7 / Issue 1 / DOI: 10.2741/A745

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Decreased mitochondrial carnitine translocase in skeletal muscles impairs utilization of fatty acids in insulin-resistant patients
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1 Institute of Protein Biochemistry and Enzymology, CNR, Naples, Italy and Department of Experimental Oncology, National Cancer Institute, Naples, Italy
2 Department of Internal Medicine, Catholic University, School of Medicine, Rome, Italy
3 Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, Bari, Italy
4 Department of Neurological Sciences, Second University of Naples
5 Scientific Department, Sigma Tau SpA, Rome, Italy
Front. Biosci. (Landmark Ed) 2002, 7(1), 109–116;
Published: 1 May 2002

Insulin resistance (IR) and its health consequences (diabetes, hypertension, cardiovascular disease, obesity etc.) affect between 25 and 35% of Westernized populations. Decreased fatty acid (FA) oxidation in skeletal muscle is implicated in obesity-related IR. Carnitine-acylcarnitine translocase (CACT) transports long-chain FAs both into mitochondria (as carnitine esters for energy-generating processes) and out of mitochondria. To determine whether CACT activity correlates with decreased FA oxidation we measured CACT concentrations in cellular and mitochondrial extracts from the skeletalmuscle of 19 obese IR individuals and of 19 lean controls. We also evaluated carnitine transport in skeletal muscle mitochondria in both groups. Mitochondrial CACT was decreased at translational and transductional level, and carnitine-carnitine and acylcarnitine-carnitine exchange rates were significantly lower in IR subjects. Aberrant acylcarnitine flux into mitochondria was not correlated with decreased activity of other components of the mitochondrial carnitine system (i.e., carnitine palmitoyl transferase-I and II). Our data suggest that by restraining entry of FA-coenzyme A into mitochondria, low CACT levels increase cytosolic FA levels and their incorporation into glycerolipids. The low level of CACT in IR muscle may contribute to the elevated muscle concentrations of triglycerides, diacylglycerol, and FA-coenzyme A characteristic of IR muscle.

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