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A high‐fat diet impairs alternative splicing of the troponin T pre‐mRNA in skeletal muscle
Author(s) -
Kimball Scot R,
Schilder Rudolf J,
Charleston Elisabeth A,
Jefferson Leonard S
Publication year - 2012
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.26.1_supplement.831.4
Subject(s) - skeletal muscle , endocrinology , medicine , obesity , rna splicing , energy homeostasis , body weight , biology , alternative splicing , troponin , messenger rna , biochemistry , gene , rna , myocardial infarction
Obesity leads to deficits in skeletal muscle function that are accompanied by reduced physical activity and energy expenditure. The basis of such deficits may originate from within the contractile apparatus, but little is known about how obesity might interfere with body weight‐induced changes in skeletal muscle composition. We recently showed that in obese Zucker rats, body weight‐appropriate alternative splicing of troponin T (TnnT3) pre‐mRNA is impaired, representative of a mismatch between body weight and skeletal muscle molecular composition. However, the generality of these finding to other models of obesity is unknown. In the present study, alternative splicing of the TnnT3 pre‐mRNA was observed within 1 wk of feeding a HFD to Sprague‐Dawley rats, even though no significant change in either body weight or composition was apparent. Moreover, changes in alternative splicing were dose‐dependent, with a greater effect observed in animals fed a diet containing 60 compared to 30 or 45 kcal% from fat. These findings represent the first evidence of nutrient‐induced regulation of alternative splicing in mammals, and suggest that early‐onset disruptions of body weight homeostasis in response to HFD may play an important role in the development of obesity. (support: NIH DK15658 (LSJ), Pennsylvania Department of Health (SRK), APS Postdoctoral Fellowship (RJS), and an APS 2011 Frontiers in Physiology Award (EAC))