Weight Loss Is Associated With Increased NAD+/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue

Author:

Rappou Elisabeth1,Jukarainen Sakari1,Rinnankoski-Tuikka Rita2,Kaye Sanna1,Heinonen Sini1,Hakkarainen Antti3,Lundbom Jesper34,Lundbom Nina3,Saunavaara Virva5,Rissanen Aila1,Virtanen Kirsi A.5,Pirinen Eija2,Pietiläinen Kirsi H.167

Affiliation:

1. Obesity Research Unit (E.R., S.J., S.K., S.H., A.R., K.H.P.), Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland

2. Research Program for Molecular Neurology (R.R.-T., E.P.), University of Helsinki, 00014 Helsinki, Finland

3. Helsinki Medical Imaging Center (A.H., J.L., N.L.), Radiology, University of Helsinki, 00290 Helsinki, Finland

4. Institute for Clinical Diabetology (J.L.), German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, 40225 Düsseldorf, Germany

5. Turku Positron Emission Tomography Center (V.S., K.A.V.), Turku University Hospital and University of Turku, 20521 Turku, Finland

6. Institute for Molecular Medicine Finland (K.H.P.), Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland

7. Endocrinology (K.H.P.), Abdominal Center, Helsinki University Hospital, University of Helsinki, 00014 Helsinki, Finland

Abstract

Abstract Context: Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs) are 2 important nicotinamide adenine dinucleotide (NAD)+-dependent enzyme families with opposing metabolic effects. Energy shortage increases NAD+ biosynthesis and SIRT activity but reduces PARP activity in animals. Effects of energy balance on these pathways in humans are unknown. Objective: We compared NAD+/SIRT pathway expressions and PARP activities in sc adipose tissue (SAT) between lean and obese subjects and investigated their change in the obese subjects during a 12-month weight loss. Design, Setting and Participants: SAT biopsies were obtained from 19 clinically healthy obese subjects (mean ± SE body mass index, 34.6 ± 2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 mo) and from 19 lean reference subjects (body mass index, 22.7 ± 1.1 kg/m2) at baseline. Main Outcome Measures: SAT mRNA expressions of SIRTs 1–7 and the rate-limiting gene in NAD+ biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT) were measured by Affymetrix, and total PARP activity by ELISA kit. Results: SIRT1, SIRT3, SIRT7, and NAMPT expressions were significantly lower, whereas total PARP activity was increased in obese compared with lean subjects. SIRT1 and NAMPT expressions increased in obese subjects between 0 and 5 months, after a mean weight loss of 11.7%. In subjects who continued to lose weight between 5 and 12 months, SIRT1 expression increased progressively, whereas in subjects with weight regain, SIRT1 reverted to baseline levels. PARP activity significantly decreased in all subjects upon weight loss. Conclusions: Calorie restriction is an attractive strategy to improve the NAD+/SIRT pathway and decrease PARPs in SAT in human obesity.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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