title: Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue.
abstract: BACKGROUND
  Mitochondrial dysfunction in adipose tissue has been implicated as a pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose tissue, chronic nutrient overload results in mitochondria driven increased reactive oxygen species (ROS) leading to carbonylation of proteins that impair mitochondrial function and downregulation of key genes linked to mitochondrial biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads to improvements in glycemic profile prior to significant weight loss. Consequently, we hypothesized that improved glycemia early after RYGB would be paralleled by decreased protein carbonylation and increased expression of genes related to mitochondrial biogenesis in adipose tissue.
  
  
  METHODS
  To evaluate this hypothesis, 16 obese individuals were studied before and 7-8 days following RYGB and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained pre- and post-bariatric surgery as well as from eight healthy, non-obese individual controls.
  
  
  RESULTS
  Prior to surgery, adipose tissue expression of PGC1α, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower expression in the obese bariatric surgery group when compared to lean controls (p < 0.05). Following RYGB, but not after AGB, patients showed significant decrease in HOMA-IR, reduction in adipose protein carbonylation, and increased expression of genes linked to mitochondrial biogenesis.
  
  
  CONCLUSIONS
  These results suggest that rapid reduction in protein carbonylation and increased mitochondrial biogenesis may explain postoperative metabolic improvements following RYGB.
authors.affiliation: Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Jahansouz
authors.affiliation: Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Federico J
authors.initials: FJ
authors.lastname: Serrot
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Brigitte I
authors.initials: BI
authors.lastname: Frohnert
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Rocio E
authors.initials: RE
authors.lastname: Foncea
authors.affiliation: Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Dorman
authors.affiliation: Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Bridget
authors.initials: B
authors.lastname: Slusarek
authors.affiliation: Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Leslie
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bernlohr
authors.affiliation: Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA. ikram001@umn.edu.
authors.forename: Sayeed
authors.initials: S
authors.lastname: Ikramuddin
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D050050:Protein Carbonylation; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; C499631:TFAM protein, human; D014157:Transcription Factors; D019001:Nitric Oxide Synthase; D003576:Electron Transport Complex IV
keywords: Adipose tissue; Adjustable gastric banding; Mitochondrial biogenesis; Protein carbonylation; Roux-en-Y gastric bypass