Received February 15, 2006
Revised March 15, 2006
Accepted after revision April 21, 2006

¹ Department of Biochemical Sciences, National Institute of Fitness and Sports

^* To whom correspondence should be addressed. E-mail: waga{at}nifs-k.ac.jp.

	Abstract

Muscle denervation induces fatty degeneration in skeletal muscle. However, the possible mechanism(s) remain to be elucidated. To gain insight into the regulation of this process, we characterized 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 isolated 5, 10, 20, and 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 alpha (C/EBPalpha) and peroxisome-proliferator activated receptor gamma2 (PPARgamma2), which play an important role in the regulation of adipocyte differentiation, was assessed by immunohistochemistry. The mRNA levels were analyzed using a real-time PCR. After muscle denervation, most muscle fibers pathologically atrophied and lipid accumulation was observed in the superficial region of the gastrocnemius muscle, suggesting that fatty degeneration occurs in our model. Both C/EBP alpha and PPARgamma2 proteins were observed in the interstitial space of denervated muscle but slightly detected in normal muscle. The expression levels of C/EBPalpha and PPARgamma2 were significantly up-regulated 30 days after muscle denervation. The expression levels of fatty acid binding protein 4 (FABP4), which reflects fatty acid metabolism, slightly decreased 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/EBPalpha and PPARgamma2.

Key Words: Denervation, Muscle