title: Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: 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; 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.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rappou
authors.affiliation: 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; 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.
authors.forename: Sakari
authors.initials: S
authors.lastname: Jukarainen
authors.affiliation: 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; 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.
authors.forename: Rita
authors.initials: R
authors.lastname: Rinnankoski-Tuikka
authors.affiliation: 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; 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.
authors.forename: Sanna
authors.initials: S
authors.lastname: Kaye
authors.affiliation: 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; 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.
authors.forename: Sini
authors.initials: S
authors.lastname: Heinonen
authors.affiliation: 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; 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.
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.affiliation: 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; 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.
authors.forename: Jesper
authors.initials: J
authors.lastname: Lundbom
authors.affiliation: 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; 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.
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.affiliation: 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; 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.
authors.forename: Virva
authors.initials: V
authors.lastname: Saunavaara
authors.affiliation: 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; 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.
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.affiliation: 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; 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.
authors.forename: Kirsi A
authors.initials: KA
authors.lastname: Virtanen
authors.affiliation: 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; 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.
authors.forename: Eija
authors.initials: E
authors.lastname: Pirinen
authors.affiliation: 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; 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.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000328:Adult; D003376:Counseling; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004038:Diet, Reducing; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D009243:NAD / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D015431:Weight Loss / Q000502:physiology*
chemical_list: D016207:Cytokines; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D011065:Poly(ADP-ribose) Polymerases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins