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

作者：Mazzatti Dawn J^*; Smith Melissa A; Oita Radu C; Lim Fei Ling; White Andrew J; Reid Michael B

来源：Physiological Genomics, 2008, 34(2): 149-161.

DOI：10.1152/physiolgenomics.00281.2007

• hindlimb suspension
• metabolic flexibility
• peroxisome proliferatoractivated receptor
• gene expression
• uncoupling protein-3
• fuel utilization
• microarray

Mazzatti DJ, Smith MA, Oita RC, Lim F-L, White AJ, Reid MB. Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPAR delta and UCP-3 expression. Physiol Genomics 34: 149-161, 2008. First published April 29, 2008; doi:10.1152/physiolgenomics.00281.2007.-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.

• 出版日期2008-7