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High Fat Diet‐Induced Alterations in Alternative Splicing of Pre‐mRNA
Author(s) -
Ravi Suhana,
Schilder Rudolf,
Jefferson Leonard,
Kimball Scot
Publication year - 2015
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.29.1_supplement.562.10
Subject(s) - rna splicing , endocrinology , medicine , exon , alternative splicing , messenger rna , gastrocnemius muscle , splice , body weight , biology , obesity , chemistry , genetics , gene , rna , skeletal muscle
Previous studies have shown that the pattern of alternative splicing of the fast troponin T ( Tnnt3 ) pre‐mRNA in gastrocnemius muscle is directly proportional to increases in both experienced body mass (i.e. actual body weight plus additional external load) and muscle force production. However, this proportionality is disrupted in obese Zucker rats, such that the muscle of obese rats expresses Tnnt3 splice forms typically observed in smaller animals. The objective of the present study was to assess the time course of development of the obesity‐induced impairment of Tnnt3 pre‐mRNA alternative splicing as a prelude to delineating the molecular mechanism(s) involved in the response. In this study, obesity‐prone Sprague Dawley rats were placed on either a control or a high‐fat diet (HFD) for up to 8 wk. There was no significant difference in body weight in rats fed the HFD compared to the control diet. However, the pattern of Tnnt3 pre‐mRNA alternative splicing was altered after only 1 wk of consuming the HFD, such that there was a mismatch between body weight and the relative abundance of Tnnt3 splice forms. Moreover, the mismatch in alternative splicing worsened with increasing time on the HFD. For example, the relative abundance of Tnnt3 pre‐mRNA present in α‐splice forms increased with increasing body weight in rats fed the control but not the HFD. Furthermore, exon array analysis identified a significant number of other pre‐mRNAs that were alternatively spliced in the gastrocnemius in response to consuming the HFD for 8 wk. Overall, the results indicate that early changes in alternative splicing associated with feeding a HFD occur prior to changes in body weight and thus are likely a direct effect of the diet. (supported by NIH grant DK094141)