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PGC1α‐1 nucleosome position in skeletal muscle of overweight individuals may determine mRNA splicing and be predictive of adiposity and hyperlipidemia (763.1)
Author(s) -
Henagan Tara,
Stewart Laura,
Johannsen Neil,
Forney Laura,
Sparks Lauren,
Church Timothy
Publication year - 2014
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.28.1_supplement.763.1
Subject(s) - skeletal muscle , dyslipidemia , endocrinology , medicine , overweight , biology , messenger rna , biomarker , obesity , gene , genetics
Epigenetic alterations, leading to aberrant metabolism and dyslipidemia, partially determine obesity and associated CVD. PGC1α is a transcriptional coactivator whose expression in skeletal muscle is decreased during obesity and CVD. Several splice variants of PGC1α are known to have similar effects on metabolism as the full length mRNA isoform (FL) and may compensate for decreased FL expression. Here, we employed scanning PCR to determine if FL and N‐truncated PGC1α (NT) mRNA splice variant expression may be epigenetically regulated through ‐1 nucleosome positioning (‐1N) in the skeletal muscle of overweight/obese, diabetic individuals. The ‐1N tended to determine splice variant mRNA expression, with a ‐1N upstream (‐1NU) in the promoter (N=9) tending to have higher FL (P=0.175) and those with a ‐1N further downstream (‐1ND; N=4) exhibited higher NT (P=0.032). The ‐1ND group had a significantly higher body fat percentage (P=0.046) and cholesterol (P=0.025) and a higher trend in LDL cholesterol (P=0.055) compared to the ‐1NU group. Importantly, ‐1N occurs upstream of changes in mRNA expression and may occur before changes in gene expression or lipids are observed. These preliminary data include a small sample size yet reveal that PGC1α ‐1N may determine mRNA splicing and serve as a predictive biomarker for the onset of obesity and adverse cardiometabolic outcomes. Grant Funding Source : Supported by NIH 5T32‐DK064584‐09, Cola‐cola Company and NIDDK R01‐068298.