Retinoic Acid Treatment Increases Lipid Oxidation Capacity in Skeletal Muscle of Mice

Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain.
Obesity (Impact Factor: 3.73). 04/2008; 16(3):585-91. DOI: 10.1038/oby.2007.104
Source: PubMed


All-trans retinoic acid (ATRA), a carboxylic form of vitamin A, favors in mice a mobilization of body fat reserves that correlates with an increment of oxidative and thermogenic capacity in adipose tissues. The objective of this study has been to investigate the effect of ATRA treatment on skeletal muscle capacity for fatty-acid catabolism.
Tissue composition and gene expression related to lipid and oxidative metabolism were analyzed in skeletal muscle of mice acutely treated with ATRA or vehicle (olive oil).
ATRA treatment triggered a dose-dependent increase in the muscle mRNA expression levels of selected enzymes, transporters and transcription factors involved in fatty-acid oxidation, respiration, and thermogenesis namely: muscle-type carnitine palmitoyltransferase 1, acyl CoA oxidase 1, subunit II of cytochrome oxidase, uncoupling protein 3, peroxisome proliferator-activated receptor-gamma co-activator -1alpha and peroxisome proliferator-activated receptor-delta (PPARdelta). The treatment also resulted in the upregulation of the mRNA levels of acetyl-CoA carboxylase 2 (ACC2), a key regulatory enzyme for mitochondrial fatty-acid oxidation in muscle. Skeletal muscle protein levels of PPARdelta and retinoid X receptor gamma, a partner for many nuclear receptors involved in lipid metabolism, were increased after ATRA treatment. Muscle lipid content was decreased.
These results indicate that ATRA treatment increases the capacity of skeletal muscle for fatty-acid oxidation. Knowledge of nutrients or nutrient-derivatives capable of enhancing oxidative metabolism in muscle and other tissues can contribute to new avenues of prevention and treatment of obesity and related disorders.

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Available from: M. Luisa Bonet, Apr 29, 2014
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    • "Retinoic acid-vitamin A metabolites exerts a number of essential biological functions through activation of two classes of nuclear receptors , RAR (α, β and γ), which respond to all-trans retinoic acid (ATRA) and 9-cis-isomers of RA; and RXR (α, β and γ), which are activated by 9-cis-RA exclusively. Studies have shown that ATRA inhibits the development of type 1 diabetes [6]; and reduces body weight and adiposity through regulation of lipid metabolism in the adipose tissue, liver and skeletal muscle of mice [7] [8] [9]. RXR agonists also have anti-diabetic effects in type 2 diabetic mouse models [10]. "
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