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Regulation of skeletal muscle Troponin T alternative splicing in response to changes in body weight is impaired in obese rodents
Author(s) -
Schilder Rudolf,
Kimball Scot,
Marden James,
Jefferson Leonard
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.341.2
Subject(s) - skeletal muscle , rna splicing , endocrinology , medicine , alternative splicing , gastrocnemius muscle , body weight , biology , obesity , gene isoform , biochemistry , gene , rna
In insects, experimental manipulation of body weight results in precise adjustment of Troponin T (TnT) expression to the imposed weight by means of mRNA alternative splicing. The objective of the present study was to test the hypothesis that this mechanism functions similarly in mammals, and is impaired in mammalian models of obesity, in which the relationship between body weight and skeletal muscle performance is disrupted. To this end, the experienced body weight of Sprague‐Dawley rats was increased 30% by fitting them with lead‐weighted vests for 7 days, after which load‐bearing gastrocnemius muscles were examined for TnT splicing patterns. Similar to previous findings in insects, the pattern of TnT mRNA splicing rapidly changed to match that of control rats with actual body weight equivalent to the load‐bearing animals. In contrast, obese Zucker rats showed an impaired TnT splicing response across a range of body weight. Based on these findings in rats, we propose that TnT alternative splicing responses to body weight are dysfunctional in mammalian obesity, causing a mismatch between body weight and skeletal muscle composition and performance. Consequently, body‐weight inappropriate skeletal muscle TnT isoform expression may result in muscle weakness, a reduction in the willingness to participate in exercise, and a reduction in the rate of energy consumption. (Supported by NIH grant DK15658)