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Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue
Elisabeth Rappou1, Sakari Jukarainen1, Rita Rinnankoski-Tuikka1
1Obesity Research Unit (E.R., S.J., S.K., S.H., A.R., K.H.P.), Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland; Research Program for Molecular Neurology (R.R.-T., E.P.), University of Helsinki, 00014 Helsinki, Finland; Helsinki Medical Imaging Center (A.H., J.L., N.L.), Radiology, University of Helsinki, 00290 Helsinki, Finland; Institute for Clinical Diabetology (J.L.), German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, 40225 Düsseldorf, Germany; Turku Positron Emission Tomography Center (V.S., K.A.V.), Turku University Hospital and University of Turku, 20521 Turku, Finland; Institute for Molecular Medicine Finland (K.H.P.), Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland; Endocrinology (K.H.P.), Abdominal Center, Helsinki University Hospital, University of Helsinki, 00014 Helsinki, Finland.
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/m(2)) during a weight-loss intervention (0, 5, and 12 mo) and from 19 lean reference subjects (body mass index, 22.7 ± 1.1 kg/m(2)) 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.
