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Journal of Lipid Research, Vol. 44, 696-704, April 2003
Copyright © 2003 by Lipid Research, Inc.

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

A. Vecchini^*, V. Ceccarelli^*, P. Orvietani^*, P. Caligiana^*, F. Susta^*, L. Binaglia^1,*, G. Nocentini, C. Riccardi and P. Di Nardo

^* Department of Internal Medicine, Section of Pharmacology, University of Perugia, Perugia, Italy
Section of Biochemistry, and Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Perugia, Italy
Laboratory of Cellular & Molecular Cardiology, Department of Internal Medicine, University of Rome "Tor Vergata," Rome, Italy

¹ To whom correspondence should be addressed. e-mail: binaglia{at}unipg.it

The hindlimb-suspended rat was used as animal model to investigate 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 15 min after 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 sterol-regulatory element binding protein (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 also affected the expression of proteins involved in lipid degradation.

In fact, the hepatic content of peroxisome proliferator-activated receptor- (PPAR) mRNA and of PPAR target genes encoding carnitine palmitoyl transferase-1 and acyl-CoA oxidase were significantly increased upon immobilization.

Abbreviations: ACC, acetyl-CoA carboxylase; ACL, ATP citrate lyase; ACO, acyl-CoA oxidase; ACS, acetyl-CoA synthase; CPT-1, carnitine palmitoyltransferase-1; FAS, fatty acid synthase; GPAT, mitochondrial glycerol-3-phosphate acyltransferase; PPAR, peroxisome proliferator-activated receptor-; SCD-1, stearoyl-CoA ⁹-desaturase-1; SREBP, sterol-regulatory element binding protein

Supplementary key words acetyl-CoA synthase • acetyl-CoA carboxylase • fatty acid synthase • 3-hydroxy-3-methylglutaryl-CoA reductase • gene expression • sterol-regulatory element binding protein • polyunsaturated fatty acid • sedentary lifestyle • immobilization

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