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Physiol. Genomics 34: 149-161, 2008. First published April 29, 2008; doi:10.1152/physiolgenomics.00281.2007
1094-8341/08 $8.00
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Received 6 December 2007; accepted in final form 25 April 2008.
Physiological Genomics 34:149-161 (2008)
1094-8341/08 $8.00 © 2008 American Physiological Society

Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPAR{delta} and UCP-3 expression

Dawn J. Mazzatti1, Melissa A. Smith2, Radu C. Oita1, Fei-Ling Lim3, Andrew J. White3 and Michael B. Reid2

1 Unilever Corporate Research, Colworth Park, Sharnbrook, Bedfordshire, United Kingdom
2 Department of Physiology, University of Kentucky, Lexington, Kentucky
3 Unilever Measurement Sciences, Colworth Park, Sharnbrook, Bedfordshire, United Kingdom

A number of physiological changes follow prolonged skeletal muscle unloading as occurs in spaceflight, bed rest, and hindlimb suspension (HLS) and also in aging. These include muscle atrophy, fiber type switching, and loss of the ability to switch between lipid and glucose usage, or metabolic inflexibility. The signaling and genomic events that precede these physiological manifestations have not been investigated in detail, particularly in regard to loss of metabolic flexibility. Here we used gene arrays to determine the effects of 24-h HLS on metabolic remodeling in mouse muscle. Acute unloading resulted in differential expression of a number of transcripts in soleus and gastrocnemius muscle, including many involved in lipid and glucose metabolism. These include the peroxisome proliferator-activated receptors (PPARs). In contrast to Ppar-{alpha} and Ppar-{gamma}, which were downregulated by acute HLS, Ppar-{delta} was upregulated concomitant with increased expression of its downstream target, uncoupling protein-3 (Ucp-3). However, differential expression of Ppar-{delta} was both acute and transient in nature, suggesting that regulation of PPAR{delta} may represent an adaptive, compensatory response aimed at regulating fuel utilization and maintaining metabolic flexibility.

hindlimb suspension; metabolic flexibility; peroxisome proliferator-activated receptor; gene expression; uncoupling protein-3; fuel utilization; microarray






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