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Intestinal adaptation to diet‐induced obesity involves an increase in intestinal epithelial stem cells but impaired stem cell function
Author(s) -
Mah Amanda,
Van Landeghem Laurianne,
Gavin Hannah,
Lund P. Kay
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.641.2
Subject(s) - stem cell , progenitor cell , microbiology and biotechnology , biology , organoid , intestinal epithelium , enteroendocrine cell , sox9 , flow cytometry , green fluorescent protein , endocrinology , medicine , epithelium , immunology , endocrine system , gene expression , hormone , biochemistry , genetics , gene
Rates of renewal of the intestinal epithelium adapt to altered nutrient intake, but the impact of diet‐induced obesity (DIO) is not well defined.. We hypothesized that DIO alters intestinal epithelial renewal and mass, and preferentially affects intestinal epithelial stem cells (IESC). Sox9‐EGFP mice permit visualization and isolation of IESC and other cells based on levels of EGFP‐reporter (IESC: Sox9‐EGFP Low; progenitors: Sox9‐EGFP Sublow; enteroendocrine cells: Sox9‐EGFP High; other differentiated cells: Sox9‐EGFP Negative). Sox9‐EGFP mice were fed high fat diet for 20 weeks to induce DIO, or low fat standard chow. Obese mice were 40% heavier than control and had 15.5% and 10.6% increase in villus height and crypt density, respectively. Histology, labeling of S‐phase cells and flow cytometry revealed that DIO increases Sox9‐EGFP Low IESC and selectively increases proliferating IESC but not progenitors. Intrinsic IESC function assessed in vitro by number of organoids formed revealed significantly fewer IESC‐derived organoids from obese mice. We conclude that in vivo , DIO increases proliferation and number of IESC resulting in increased functional epithelial mass. However DIO impairs intrinsic IESC survival or growth indicating detrimental effects of DIO on IESC that may be compensated by extrinsic in vivo factors that promote IESC hyperproliferation. Grants: NIH DK040247–19, NIH 2‐T32‐DK07686 Grant Funding Source : NIH