J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on April 1, 2003

Papers In Press, published online ahead of print January 16, 2003
J. Lipid Res., doi:10.1194/jlr.M200252-JLR200
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Submitted on July 2, 2002
Revised on December 4, 2002
Accepted on January 3, 2003

Enhanced expression of hepatic lipogenic enzymes in an animal model of sedentariness

A. Vecchini, V. Ceccarelli, P. Orvietani, P. Caligiana, F. Susta, L. Binaglia, G. Nocentini, C. Riccardi, and P. Di Nardo

Internal Medicine, University of Perugia, Perugia 06126

Corresponding Author: binaglia{at}unipg.it

The hindlimb-suspended rat was used as animal model to investigate on the effects induced by immobilization of the skeletal muscle in the expression of the genes encoding hepatic lipogenic enzymes. Following a 14 day-period of immobilization, rats were injected intraperitoneally with radioactive acetate and the labeling of hepatic lipids and cholesterol was evaluated after 15 min from the isotope injection. The incorporation of labeled acetate in lipids and cholesterol was almost three times higher in the liver of immobilized rats than in control animals, as a consequence of the enhanced transcription of the genes encoding acetyl-CoA synthase, acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoA reductase. The high expression of the key-enzymes for fatty acid and cholesterol synthesis induced by immobilization was not paralleled by an increase of the hepatic SREBP-1 and SREBP-2 mRNA content. However, the expression of the mature form of SREBP-1 and SREBP-2 was higher in the nuclear fraction of immobilized rat liver than in controls, due to a significant increase of the cleavage of the native proteins. Immobilization affected also the expression of proteins involved in lipid degradation. In fact, the hepatic content of PPARa mRNA and of PPARa target genes encoding carnitine palmitoyl transferase-1 and acyl-CoA oxidase were significantly increased upon immobilization.


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