High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates with Obesity and Insulin Resistance in Mouse
Open accessAbstract
BACKGROUND: Obesity induced by high fat (HF) diet is associated with inflammation which contributes to development of insulin resistance. Most prior studies have focused on adipose tissue as the source of obesity-associated inflammation. Increasing evidence links intestinal bacteria to development of diet-induced obesity (DIO). This study tested the hypothesis that HF western diet and gut bacteria interact to promote intestinal inflammation, which contributes to the progression of obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: Conventionally raised specific-pathogen free (CONV) and germ-free (GF) mice were given HF or low fat (LF) diet for 2-16 weeks. Body weight and adiposity were measured. Intestinal inflammation was assessed by evaluation of TNF-alpha mRNA and activation of a NF-kappaB(EGFP) reporter gene. In CONV but not GF mice, HF diet induced increases in body weight and adiposity. HF diet induced ileal TNF-alpha mRNA in CONV but not GF mice and this increase preceded obesity and strongly and significantly correlated with diet induced weight gain, adiposity, plasma insulin and glucose. In CONV mice HF diet also resulted in activation of NF-kappaB(EGFP) in epithelial cells, immune cells and endothelial cells of small intestine. Further experiments demonstrated that fecal slurries from CONV mice fed HF diet are sufficient to activate NF-kappaB(EGFP) in GF NF-kappaB(EGFP) mice. CONCLUSIONS/SIGNIFICANCE: Bacteria and HF diet interact to promote proinflammatory changes in the small intestine, which precede weight gain and obesity and show strong and significant associations with progression of obesity and development of insulin resistance. To our knowledge, this is the first evidence that intestinal inflammation is an early consequence of HF diet which may contribute to obesity and associated insulin resistance. Interventions which limit intestinal inflammation induced by HF diet and bacteria may protect against obesity and insulin resistance.
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Germ-free mice are protected from diet-induced obesity when fed a Western-style diet.
“Germ-free mice are protected from diet-induced obesity when fed a Western-style diet8–10”
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- Authors
- Ding, S., Chi, M. M., Scull, B. P., Rigby, R., Schwerbrock, N. M. J., Magness, S., Jobin, C., & Lund, P. K.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Vanderbilt University Medical Center (US)
- Lancaster University (GB)
- Corresponding author
- Ding, Shengli
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-08-16
- Volume
- 5
- Issue
- 8
- Pages
- e12191
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2922379
- OpenAlex
- W2086648828
- Cited by
- 713
- References
- 34
- Citations by year
- 2026: 23 · 2025: 26 · 2024: 39 · 2023: 46 · 2022: 50 · 2021: 59 · 2020: 53 · 2019: 54 · 2018: 46 · 2017: 52 · 2016: 59 · 2015: 66 · 2014: 45 · 2013: 38 · 2012: 31
- FWCI
- 11.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lancaster EPrints (Lancaster University) (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UNC Libraries
- Funders
- Gillings School of Public Health
- National Institute of Mental Health (T32MH075854)
- National Institute of Environmental Health Sciences (P30ES10126), P30ES010126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- high-fat diet, diet-induced obesity, insulin resistance, intestinal inflammation, gut microbiota, germ-free mice, TNF-α, NF-κB activation, small intestine, Western diet, adiposity
- MeSH terms
- Adipose Tissue, Animals, Bacteria, Body Weight, Dietary Fats, Gene Expression Regulation, Inflammation, Insulin Resistance, Intestinal Mucosa, Intestines, Mice, Inbred C57BL, Obesity, RNA, Messenger, Specific Pathogen-Free Organisms, Tumor Necrosis Factor-alpha, Biomarkers, NF-kappa B, Mice
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