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High‐fat diet induced expansion of colon crypt epithelial proliferative zone towards lumen correlates with elevated innate inflammatory markers in the human‐relevant porcine model (123.2)
Author(s) -
Vanamala Jairam,
Radhakrishnan Sridhar,
Eriksson Elisabeth,
Charepalli Venkata,
Kim Sung,
Reddivari Lavanya
Publication year - 2014
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.28.1_supplement.123.2
Subject(s) - crypt , inflammation , colorectal cancer , immunohistochemistry , infiltration (hvac) , medicine , proliferation index , endocrinology , biology , cancer , physics , thermodynamics
Recent evidence shows that high‐fat diet (HFD) alone causes colon cancer in mice; however, underlying mechanisms are not fully elucidated. An expansion of proliferative zone towards the crypt lumen is a biomarker for colon cancer in animal models and humans. We hypothesized that HFD induced expansion of colonic proliferative zone and elevation of proliferating index correlates with innate inflammatory markers in the porcine model that has similar gastrointestinal function/physiology as humans. Pigs (n = 8/group) were provided either standard diet (SD; 5% fat) or HFD (25% fat) for 13 wk. HFD elevated proliferative zone (Ki‐67; immunofluorescence; p = 0.02) and proliferative index (p = 0.06). HFD numerically increased (p = 0.15) distal colon expression of pattern recognition receptors TLRs 2/4 and TLR‐4 responsive genes NF‐κB, COX‐2 and TNF‐α (qPCR) compared to SD group. However, HFD elevated proliferative zone correlated with TLR‐4, NF‐κB, COX‐2 and TNF‐α expression (r = 0.77, 0.71, 0.78 and 0.62, respectively, p = 0.02). HFD group had greater distal colon macrophage infiltration (mac387; immunohistochemistry; p = 0.1) that correlated with TLR‐4 expression (r = 0.52, p = 0.05). As proliferating colonocytes are highly susceptible to damage due to oxidative stress/inflammation, expanded proliferative zone may partly explain how chronic HFD consumption causes colon cancer. Grant Funding Source : Supported by USDA‐NIFA NRI Grant 2009‐55200‐05197