Dataset Information

PARP-2 regulates SIRT1 expression and whole-body energy expenditure.

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.

SUBMITTER: Bai P

PROVIDER: S-EPMC3108571 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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PARP-2 regulates SIRT1 expression and whole-body energy expenditure.

Bai Péter P Canto Carles C Brunyánszki Attila A Huber Aline A Szántó Magdolna M Cen Yana Y Yamamoto Hiroyasu H Houten Sander M SM Kiss Borbala B Oudart Hugues H Gergely Pál P Menissier-de Murcia Josiane J Schreiber Valérie V Sauve Anthony A AA Auwerx Johan J

Cell metabolism 20110401 4

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 r ...[more]

PMID: 21459329

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Project description:BackgroundAccurate assessment of energy expenditure may support weight-management recommendations. Measuring energy expenditure for each postpartum woman is unfeasible; therefore, accurate predictive equations are needed.ObjectivesThis study compared measured with predicted resting energy expenditure (REE) and total energy expenditure (TEE) in postpartum women.MethodsThis was a longitudinal observational study. REE was measured at 3 mo postpartum (n = 52) and 9 mo postpartum (n = 49), whereas TEE was measured once at 9 mo postpartum (n = 43) by whole body calorimetry (WBC). Measured REE (REEWBC) was compared with 17 predictive equations; measured TEE plus breast milk energy output (ERWBC) was compared with the estimated energy requirements/Dietary Reference Intakes equation (EERDRI). Fat and fat-free mass were measured by dual-energy X-ray absorptiometry. Group-level agreement was assessed by the Pearson correlation, paired t test, and Bland-Altman (bias) analyses. Individual-level accuracy was assessed with the use of Bland-Altman limits of agreement, and by the percentage of women with predicted energy expenditure within 10% of measured values ("accuracy").ResultsThe cohort was primarily Caucasian (90%). At a group level, the best equation predicting REEWBC was the DRI at 3 mo postpartum (-7 kcal, -0.1%; absolute and percentage bias, respectively), and the Harris-Benedict at 9 mo postpartum (-17 kcal, -0.5%). At an individual level, the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) height and weight equation was the most accurate at 3 mo postpartum (100% accuracy) and 9 mo postpartum (98% accuracy), with the smallest limits of agreement. Equations including body composition variables were not more accurate. Compared with ERWBC, EERDRI bias was -36 kcal, with inaccurate predictions in 33% of women.ConclusionsMany REE predictive equations were accurate for group assessment, with the FAO/WHO/UNU height and weight equation having the highest accuracy for individuals. EERDRI performed well at a group level, but inaccurately for 33% of women. A greater understanding of the physiology driving energy expenditure in the postpartum period is needed to better predict TEE and ultimately guide effective weight-management recommendations.

Dataset Information

PARP-2 regulates SIRT1 expression and whole-body energy expenditure.

Publications

PARP-2 regulates SIRT1 expression and whole-body energy expenditure.

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