There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although
originally described as a DNA repair protein, has a widespread role as a metabolic
regulator. We show that the ablation of PARP2 induced characteristic changes in the
lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding
protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle.
Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone,
an anabolic steroid. Thus, skeletal muscle fibers in PARP2(-/-) mice were stronger
compared to those of their wild-type littermates. In addition, we detected changes
in the dynamics of the cell membrane, suggesting that lipidome changes also affect
the biophysical characteristics of the cell membrane. In in silico and wet chemistry
studies, we identified lipid species that can decrease the expression of PARP2 and
potentially phenocopy the genetic abruption of PARP2, including artificial steroids.
In view of these observations, we propose a new role for PARP2 as a lipid-modulated
regulator of lipid metabolism.
