Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2014, Article ID 895734, 7 pages
http://dx.doi.org/10.1155/2014/895734
Research Article

PGC1α −1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals

1Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA
2Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO 80639, USA
3School of Kinesiology, Louisiana State University, Baton Rouge, LA 70803, USA
4Florida Hospital Sanford-Burnham Translational Research Institute for Metabolism and Diabetes, Orlando, FL 32804, USA
5Laboratory of Preventative Medicine, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA

Received 31 July 2014; Accepted 26 November 2014; Published 28 December 2014

Academic Editor: Brian N. Finck

Copyright © 2014 Tara M. Henagan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

PGC1, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1 undergoes splicing to produce several mRNA variants, with the NTPGC1 variant having a similar biological function to the full length PGC1 (FLPGC1). 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 expression. PGC1 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  −1 nucleosome (−1N) position is associated with splice variant NTPGC1 but not FLPGC1 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 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 splice variant expression, and −1N position and NTPGC1 variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.