A one and a two … expanding roles for poly(ADP-ribose) polymerases in metabolism

Abstract

In two related papers in this issue, Bai et al. (2011a, 2011b) observe that PARP-1- or PARP-2-deficient mice show increased energy expenditure and protection against diet-induced obesity. This metabolic phenotype is achieved, in part, through SIRT1 activation, either by increasing NAD(+) levels or by promoting SIRT1 expression.

Figure 1. Studies with PARP-1^−/− and PARP-2^−/− mice illustrate essential roles for PARP-1 and PARP-2 in metabolic homeostasis and reveal several potential modes of functional interplay with SIRT1

(A) The schematic summarizes the effects of PARP-1 or PARP-2 knockout on a variety of metabolism-related phenotypes in five different tissues. The effects (increase or decrease upon knockout) are illustrated by the use of color-coded arrows (PARP-1, red; PARP-2, blue). Many of the effects illustrated here are based on the two papers by Bai et al., but information from other recent papers is included as well. The phenotypes shown for PARP-1 are based on PARP-1^−/− mice with a predominantly C57BL/6J background. Opposite effects for some parameters may be noted for PARP-1^−/− mice made in a predominantly SV129 background (see the text). (B) Potential mechanisms for functional interplay and potential antagonism between PARP-1 or PARP-2 and SIRT1. The schematic illustrates four different modes of functional interplay and potential antagonism between PARP-1 or PARP-2 (collectively labeled “PARP”) and SIRT1, labeled a through d.