Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation
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Consumption of diets high in fat and calories leads to hyperphagia and obesity, which is associated with chronic “low-grade” systemic inflammation. Ingestion of a high-fat diet alters the gut microbiota, pointing to a possible role in the development of obesity. The present study used Sprague-Dawley rats that, when fed a high-fat diet, exhibit either an obesity-prone (DIO-P) or obesity-resistant (DIO-R) phenotype, to determine whether changes in gut epithelial function and microbiota are diet or obese associated. Food intake and body weight were monitored daily in rats maintained on either low- or high-fat diets. After 8 or 12 wk, tissue was removed to determine adiposity and gut epithelial function and to analyze the gut microbiota using PCR. DIO-P but not DIO-R rats exhibit an increase in toll-like receptor (TLR4) activation associated with ileal inflammation and a decrease in intestinal alkaline phosphatase, a luminal enzyme that detoxifies lipopolysaccharide (LPS). Intestinal permeability and plasma LPS were increased together with phosphorylation of myosin light chain and localization of occludin in the cytoplasm of epithelial cells. Measurement of bacterial 16S rRNA showed a decrease in total bacterial density and an increase in the relative proportion of Bacteroidales and Clostridiales orders in high-fat-fed rats regardless of phenotype; an increase in Enterobacteriales was seen in the microbiota of DIO-P rats only. Consumption of a high-fat diet induces changes in the gut microbiota, but it is the development of inflammation that is associated with the appearance of hyperphagia and an obese phenotype.
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Consumption of a high-fat diet may induce unfavorable changes in the gut microbiota.
“Thus, consumption of a high-fat diet may also induce unfavorable changes in the gut microbiota [149].”
From Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes (2016) · cites this paper as [149]
Inflammation is closely associated with the presence or absence of these microbes (Clostridiales and Lactobacillaceae).
“Previous studies have shown a close association between inflammation and the presence or absence of these microbes, respectively,62–64”
From Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases (2015) · cites this paper as [62]
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- Authors
- de La Serre, C. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., & Raybould, H. E.
- Affiliations
- Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis;
- University of California, Davis (US)
- Corresponding author
- Raybould, Helen E.
- ORCID
- Raybould, Helen E.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2010-08
- Volume
- 299
- Issue
- 2
- Pages
- G440-G448
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- PMC
- PMC2928532
- OpenAlex
- W2140598936
- Cited by
- 949
- References
- 40
- Citations by year
- 2026: 24 · 2025: 32 · 2024: 61 · 2023: 48 · 2022: 72 · 2021: 81 · 2020: 58 · 2019: 88 · 2018: 65 · 2017: 72 · 2016: 65 · 2015: 71 · 2014: 56 · 2013: 60 · 2012: 53
- FWCI
- 20.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r43hl055064-01)
- National Heart, Lung, and Blood Institute (HL-55064)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK041004, DK 41004)
- 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, gut microbiota, intestinal inflammation, TLR4, intestinal permeability, lipopolysaccharide, intestinal epithelial barrier, occludin, myosin light chain phosphorylation, Bacteroidales, Clostridiales, Enterobacterales, hyperphagia, low-grade inflammation
- MeSH terms
- Alkaline Phosphatase, Animals, Body Weight, Dietary Fats, Disease Susceptibility, Eating, Enteritis, Hyperphagia, Intestinal Mucosa, Intestines, Lipopolysaccharides, Male, Membrane Proteins, Peroxidase, Obesity, Permeability, Rats, Sprague-Dawley, Tight Junctions, Adiposity, Toll-Like Receptor 4, Rats, Metagenome
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