title: Diet and gastrointestinal bypass-induced weight loss: the roles of ghrelin and peptide YY.
abstract: OBJECTIVE
  Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). To evaluate PYY's role in mediating weight loss post-GIBP, we undertook GIBP surgery in PyyKO mice.
  
  
  METHODS
  Male C57BL/6 mice randomized to a high-fat diet or control diet were killed at 4-week intervals. DIO mice underwent switch to ad libitum low-fat diet (DIO-switch) or caloric restriction (CR) for 4 weeks before being killed. PyyKO mice and their DIO wild-type (WT) littermates underwent GIBP or sham surgery and were culled 10 days postoperatively. Fasting acyl-ghrelin, total PYY, active GLP-1 concentrations, stomach ghrelin expression, and colonic Pyy and glucagon expression were determined. Fasting and postprandial PYY and GLP-1 concentrations were assessed 30 days postsurgery in GIBP and sham pair-fed (sham.PF) groups.
  
  
  RESULTS
  DIO progressively reduced circulating fasting acyl-ghrelin, PYY, and GLP-1 levels. CR and DIO-switch caused weight loss but failed to restore circulating PYY to weight-appropriate levels. After GIBP, WT mice lost weight and exhibited increased circulating fasting PYY and colonic Pyy and glucagon expression. In contrast, the acute effects of GIBP on body weight were lost in PyyKO mice. Fasting PYY and postprandial PYY and GLP-1 levels were increased in GIBP mice compared with sham.PF mice.
  
  
  CONCLUSIONS
  PYY plays a key role in mediating the early weight loss observed post-GIBP, whereas relative PYY deficiency during dieting may compromise weight-loss attempts.
authors.affiliation: Centre for Obesity Research, Department of Medicine, University College London, Rayne Institute, London, UK.
authors.forename: Keval
authors.initials: K
authors.lastname: Chandarana
authors.forename: Cigdem
authors.initials: C
authors.lastname: Gelegen
authors.forename: Efthimia
authors.initials: E
authors.lastname: Karra
authors.forename: Agharul I
authors.initials: AI
authors.lastname: Choudhury
authors.forename: Megan E
authors.initials: ME
authors.lastname: Drew
authors.forename: Veronique
authors.initials: V
authors.lastname: Fauveau
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Andreelli
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Withers
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Batterham
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003106:Colon / Q000378:metabolism; D018752:Diet, Fat-Restricted; D004038:Diet, Reducing; D004797:Enzyme-Linked Immunosorbent Assay; D015390:Gastric Bypass; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism* / Q000601:surgery*; D019894:Peptide YY / Q000378:metabolism*; D011863:Radioimmunoassay; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015431:Weight Loss / Q000502:physiology*
chemical_list: D054439:Ghrelin; D020738:Leptin; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D005934:Glucagon