PMID- 23776529 OWN - NLM STAT- MEDLINE DCOM- 20140116 LR - 20220311 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 6 DP - 2013 TI - Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats. PG - e65696 LID - 10.1371/journal.pone.0065696 [doi] LID - e65696 AB - BACKGROUND AND AIMS: 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. FAU - Hansen, Carl Frederik AU - Hansen CF AD - Department of Histology, Gubra, Horsholm, Denmark ; Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark. FAU - Bueter, Marco AU - Bueter M FAU - Theis, Nadine AU - Theis N FAU - Lutz, Thomas AU - Lutz T FAU - Paulsen, Sarah AU - Paulsen S FAU - Dalboge, Louise S AU - Dalboge LS FAU - Vrang, Niels AU - Vrang N FAU - Jelsing, Jacob AU - Jelsing J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130611 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 106388-42-5 (Peptide YY) RN - 55963-74-1 (Proglucagon) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - Enteroendocrine Cells/*cytology/metabolism MH - Gastric Bypass/*adverse effects MH - Glucagon-Like Peptide 1/genetics/metabolism MH - Hypertrophy/etiology/*physiopathology MH - Male MH - Mucous Membrane/metabolism MH - Peptide YY/genetics/metabolism MH - Proglucagon/genetics/metabolism MH - Rats MH - Rats, Wistar PMC - PMC3679162 COIS- Competing Interests: The following authors are currently employed by the commercial company Gubra Aps: Niels Vrang, Louise Schjellerup Dalboge, Sarah Paulsen, Jacob Jelsing and Carl Frederik Hansen. However, this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2013/06/19 06:00 MHDA- 2014/01/17 06:00 PMCR- 2013/06/11 CRDT- 2013/06/19 06:00 PHST- 2012/11/09 00:00 [received] PHST- 2013/04/29 00:00 [accepted] PHST- 2013/06/19 06:00 [entrez] PHST- 2013/06/19 06:00 [pubmed] PHST- 2014/01/17 06:00 [medline] PHST- 2013/06/11 00:00 [pmc-release] AID - PONE-D-12-34899 [pii] AID - 10.1371/journal.pone.0065696 [doi] PST - epublish SO - PLoS One. 2013 Jun 11;8(6):e65696. doi: 10.1371/journal.pone.0065696. Print 2013.