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

Abstract EN

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, identifier NCT00458133.