PGC1α −1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals. (25th December 2014)

• Record Type: Journal Article
• Authors: Henagan, Tara M.; Stewart, Laura K.; Forney, Laura A.; Sparks, Lauren M.; Johannsen, Neil; Church, Timothy S.
• Other Names: Finck Brian N. Academic Editor.
• Is Part Of: PPAR research. Volume 2014(2014)
• Publication Date: 2014-12-25
• Subjects: Peroxisomes -- Periodicals; Peroxisomal disorders -- Periodicals; 571.65505
• DOI: 10.1155/2014/895734
• Languages: English
• ISSNs: 1687-4757

Abstract

Abstract : PGC1 α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1 α undergoes splicing to produce several mRNA variants, with the NTPGC1 α variant having a similar biological function to the full length PGC1 α ( FLPGC1 α ). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1 α expression. PGC1 α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1 α −1 nucleosome (−1N) position is associated with splice variant NTPGC1 α but not FLPGC1 α expression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP) expressed lower levels of NTPGC1 α than those with the −1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator of NTPGC1 α splice variant expression, and −1N position and NTPGC1 α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifierNCT00458133 .