High Fat Diet Alters Gut Microbiota and the Expression of Paneth Cell-Antimicrobial Peptides Preceding Changes of Circulating Inflammatory Cytokines.
Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined. The compositions of gut microbiota were altered at 8 wk HF feeding, followed with reduced Paneth antimicrobial peptides lysozyme and Reg IIIγafter 12 and 16 wk HF feeding (p< 0.05), whereas elevations of circulating inflammatory cytokines IFNγand TNF-αwere observed until feeding a HF diet for 16 weeks (p< 0.05). These results indicated that high fat diet may stimulate intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines. These findings emphasized the importance of microbiota, in addition to adipose tissue per se, in driving intestinal inflammation, which may thereafter promote intestinal tumorigenesis.
School of Pharmacy and Biological Engineering, Chengdu University, Sichuan, China; School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
Xiulan
0000-0003-2511-252X
X
Guo
School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
Jinchao
J
Li
School of Pharmacy and Biological Engineering, Chengdu University, Sichuan, China.
Renyong
R
Tang
Department of Food Science, University of Massachusetts, Amherst, MA, USA.
Guodong
G
Zhang
Grand Forks Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Grand Forks, ND, USA.
Huawei
H
Zeng
School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
Richard J
RJ
Wood
School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
Zhenhua
0000-0001-8439-055X
Z
Liu
D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D000069196:Gastrointestinal Microbiome / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000276:immunology / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D010455:Peptides; C519253:Ang4 protein, mouse; D012259:Ribonuclease, Pancreatic; D009113:Muramidase