title: Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins.
abstract: BACKGROUND
  Sirtuins (SIRTs) regulate cellular metabolism and mitochondrial function according to the energy state of the cell reflected by NAD(+) levels.
  
  
  OBJECTIVE
  Our aim was to determine whether expressions of SIRTs and NAD(+) biosynthesis genes are affected by acquired obesity and how possible alterations are connected with metabolic dysfunction while controlling for genetic and familial factors.
  
  
  METHODS
  We studied a cross-sectional sample of 40 healthy pairs of monozygotic twins, including 26 pairs who were discordant for body mass index (within-pair difference > 3 kg/m(2)), from the FinnTwin12 and FinnTwin16 cohorts.
  
  
  METHODS
  Subcutaneous adipose tissue (SAT) transcriptomics was analyzed by using Affymetrix U133 Plus 2.0 chips, total SAT (poly-ADP) ribose polymerase (PARP) activity by an ELISA kit, body composition by dual-energy x-ray absorptiometry and magnetic resonance imaging/spectroscopy, and insulin sensitivity by an oral glucose tolerance test.
  
  
  RESULTS
  SIRT1, SIRT3, SIRT5, NAMPT, NMNAT2, NMNAT3, and NRK1 expressions were significantly down-regulated and the activity of main cellular NAD(+) consumers, PARPs, trended to be higher in the SAT of heavier co-twins of body mass index-discordant pairs. Controlling for twin-shared factors, SIRT1, SIRT3, NAMPT, NMNAT3, and NRK1 were significantly negatively correlated with adiposity, SIRT1, SIRT5, NMNAT2, NMNAT3, and NRK1 were negatively correlated with inflammation, and SIRT1 and SIRT5 were positively correlated with insulin sensitivity. Expressions of genes involved in mitochondrial unfolded protein response were also significantly down-regulated in the heavier co-twins.
  
  
  CONCLUSIONS
  Our data highlight a strong relationship of reduced NAD(+)/SIRT pathway expression with acquired obesity, inflammation, insulin resistance, and impaired mitochondrial protein homeostasis in SAT.
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Sakari
authors.initials: S
authors.lastname: Jukarainen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Sini
authors.initials: S
authors.lastname: Heinonen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Rämö
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Rita
authors.initials: R
authors.lastname: Rinnankoski-Tuikka
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rappou
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Mark
authors.initials: M
authors.lastname: Tummers
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Maheswary
authors.initials: M
authors.lastname: Muniandy
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Jesper
authors.initials: J
authors.lastname: Lundbom
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Eija
authors.initials: E
authors.lastname: Pirinen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity (S.J., S.H., J.T.R., E.R., M.T., M.M., A.R., K.H.P.), FIMM, Institute for Molecular Medicine Finland, (J.T.R., J.K., K.H.P.), Molecular Neurology, Research Programs Unit (R.R.T., E.P.), University of Helsinki, Helsinki, Finland, and Helsinki Medical Imaging Center, Radiology (A.H., N.L.), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland 00014; Institute for Clinical Diabetology, German Diabetes Center (J.L.), Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany; Finnish Twin Cohort Study, Department of Public Health (J.K.), and Department of Health (J.K.), National Institute for Health and Welfare, Helsinki, Finland; and Department of Endocrinology, Abdominal Center (K.H.P.), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 00014.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008019:Life Style; D008297:Male; D009243:NAD / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014430:Twins, Monozygotic
chemical_list: D009243:NAD; D037761:Sirtuins