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and PPAR
2 in denervated muscle
1 Department of Biochemical Sciences, National Institute of Fitness and Sports, 1 Shiromizu, Kanoya, Kagoshima 891-2393, Japan
Muscle denervation induces fatty degeneration in skeletal muscle. However, the possible mechanism(s) remains to be elucidated. To gain insight into the regulation of this process, this study was designed to characterize the expression pattern of genes encoding transcriptional factors that regulate adipogenesis and the terminal differentiation marker of adipocytes in denervated muscle. Female mice underwent surgery to transect the sciatic nerve, and then the gastrocnemius muscles were harvested 5, 10, 20 or 30 days after surgery. The extent of fatty degeneration was assessed as lipid accumulation by Oil Red O staining. The cellular localization of CCCAT/enhancer-binding protein
(C/EBP
) and peroxisome proliferator-activated receptor
2 (PPAR
2), which play an important role in the regulation of adipocyte differentiation, was assessed by immunohistochemistry. The mRNA levels were analysed using a real-time polymerase chain reaction. After muscle denervation, most muscle fibres atrophied pathologically, and lipid accumulation was observed in the superficial region of the gastrocnemius muscle, suggesting that fatty degeneration occurs in this model. Both C/EBP
and PPAR
2 proteins were observed in the interstitial space of denervated muscle but detected in small amounts in normal muscle. The expression levels of C/EBP
and PPAR
2 were significantly upregulated 30 days after muscle denervation. The expression levels of fatty acid binding protein 4 (FABP4), which reflects fatty acid metabolism, were decreased slightly at 5 and 10 days and then returned to control levels 30 days after muscle denervation. These findings suggest that muscle denervation-induced fatty degeneration may be mediated through C/EBP
and PPAR
2.
(Received 15 February 2006;
accepted after revision 7 April 2006; first published online 21 April 2006)
Corresponding author A. Wagatsuma: Department of Biochemical Sciences, National Institute of Fitness and Sports, 1 Shiromizu, Kanoya, Kagoshima 891-2393, Japan. Email: waga{at}nifs-k.ac.jp
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