Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis.

There is a growing body of evidence that poly(ADP-ribose) polymerase-2 although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of induced characteristic changes in the lipidome. The silencing of Pduanyu372 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 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 Pduanyu372 and potentially phenocopy the genetic abruption of including artificial steroids. In view of these observations, we propose a new role for Pduanyu372 as a lipid-modulated regulator of lipid metabolism.

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