Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPARdelta and UCP-3 expression.
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 PPARdelta may represent an adaptive, compensatory response aimed at regulating fuel utilization and maintaining metabolic flexibility.
Mazzatti
Dawn J
DJ
Unilever Corporate Research, Colworth Park, Sharnbrook, Bedfordshire, United Kingdom. dawn.mazzatti@unilever.com
Smith
Melissa A
MA
Oita
Radu C
RC
Lim
Fei-Ling
FL
White
Andrew J
AJ
Reid
Michael B
MB
D000818:Animals; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D019417:Hindlimb Suspension; D007473:Ion Channels / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D000071247:Uncoupling Protein 3
D007473:Ion Channels; D024101:Mitochondrial Proteins; D047494:PPAR delta; D012333:RNA, Messenger; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D005947:Glucose