PARP-2 regulates SIRT1 expression and whole-body energy expenditure. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line
  • Dietary Fats
  • Energy Metabolism
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Glucose Intolerance
  • Humans
  • Insulin Resistance
  • Mice
  • Mice, Knockout
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering

MeSH Major

  • Poly(ADP-ribose) Polymerases
  • Sirtuin 1

abstract

  • SIRT1 is a NAD(+)-dependent enzyme that affects metabolism by deacetylating key transcriptional regulators of energy expenditure. Here, we tested whether deletion of PARP-2, an alternative NAD(+)-consuming enzyme, impacts on NAD(+) bioavailability and SIRT1 activity. Our results indicate that PARP-2 deficiency increases SIRT1 activity in cultured myotubes. However, this increase was not due to changes in NAD(+) levels, but to an increase in SIRT1 expression, as PARP-2 acts as a direct negative regulator of the SIRT1 promoter. PARP-2 deletion in mice increases SIRT1 levels, promotes energy expenditure, and increases mitochondrial content. Furthermore, PARP-2(-/-) mice were protected against diet-induced obesity. Despite being insulin sensitized, PARP-2(-/-) mice were glucose intolerant due to a defective pancreatic function. Hence, while inhibition of PARP activity promotes oxidative metabolism through SIRT1 activation, the use of PARP inhibitors for metabolic purposes will require further understanding of the specific functions of different PARP family members. Copyright © 2011 Elsevier Inc. All rights reserved.

publication date

  • April 6, 2011

has subject area

  • Animals
  • Cell Line
  • Dietary Fats
  • Energy Metabolism
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Glucose Intolerance
  • Humans
  • Insulin Resistance
  • Mice
  • Mice, Knockout
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering
  • Sirtuin 1

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3108571

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2011.03.013

PubMed ID

  • 21459329

Additional Document Info

start page

  • 450

end page

  • 460

volume

  • 13

number

  • 4