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

• Published in: Journal of lipid research 2003-04, Vol.44 (4), p.696-704
• Main Authors: Vecchini, A, Ceccarelli, V, Orvietani, P, Caligiana, P, Susta, F, Binaglia, L, Nocentini, G, Riccardi, C, Di Nardo, P
• Format: Article
• Language: English
• Subjects: 3-hydroxy-3-methylglutaryl-CoA reductase; Acetates - metabolism; acetyl-CoA carboxylase; acetyl-CoA synthase; Animals; CCAAT-Enhancer-Binding Proteins - analysis; Cholesterol - biosynthesis; DNA-Binding Proteins - analysis; Enzymes - genetics; fatty acid synthase; gene expression; Immobilization - physiology; Lipids - analysis; Lipids - biosynthesis; Liver - chemistry; Liver - enzymology; Male; Models, Animal; Rats; Rats, Wistar; RNA, Messenger - analysis; Sterol Regulatory Element Binding Protein 1; sterol-regulatory element binding protein; Transcription Factors - analysis
• ISSN: 0022-2275
• DOI: 10.1194/jlr.m200252-jlr200

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-alpha (PPARalpha) mRNA and of PPARalpha target genes encoding carnitine palmitoyl transferase-1 and acyl-CoA oxidase were significantly increased upon immobilization.