title: Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats.
abstract: OBJECTIVE
  Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal.
  
  
  METHODS
  The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells.
  
  
  RESULTS
  RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell.
  
  
  CONCLUSIONS
  Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB.
authors.affiliation: Department of Histology, Gubra, Hørsholm, Denmark ; Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Carl Frederik
authors.initials: CF
authors.lastname: Hansen
authors.forename: Marco
authors.initials: M
authors.lastname: Bueter
authors.forename: Nadine
authors.initials: N
authors.lastname: Theis
authors.forename: Thomas
authors.initials: T
authors.lastname: Lutz
authors.forename: Sarah
authors.initials: S
authors.lastname: Paulsen
authors.forename: Louise S
authors.initials: LS
authors.lastname: Dalbøge
authors.forename: Niels
authors.initials: N
authors.lastname: Vrang
authors.forename: Jacob
authors.initials: J
authors.lastname: Jelsing
mesh_terms: D000818:Animals; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000378:metabolism; D015390:Gastric Bypass / Q000009:adverse effects*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D006984:Hypertrophy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D019894:Peptide YY / Q000235:genetics / Q000378:metabolism; D052336:Proglucagon / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019894:Peptide YY; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1