ArticleBMC medical genomics2008
The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice.
Article in BMC medical genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 186 citations in OpenAlex.
- Varietal Differences in Kidney Beans Modulate Gut Microbiota and Inflammation During High-Fat Diet-Induced Obesity in Male Mice.Nutrients · 2026Article
- A Low-Cost, High-Fat Diet Effectively Induces Obesity and Metabolic Alterations and Diet Normalization Modulates Microbiota in C57BL/6 Mice.Nutrients · 2025Article
- Anti-Oxidative and Anti-Inflammatory Effect of Protaetia Brevitarsis-Derived Protein Hydrolysates in Adipose Tissues of Obese Mice.International journal of molecular sciences · 2025Article
- Exercise alters transcriptional profiles of senescence and gut barrier integrity in intestinal crypts of aging mice.npj aging · 2025Article
- Intestinal antibody repertoire is altered by diabetes and varies depending on the pathogenesis.Biochemistry and biophysics reports · 2025Article
- Multitissue single-cell analysis reveals differential cellular and molecular sensitivity between fructose and high-fat high-sucrose diets.Cell reports · 2025Article
- Review Article on Molecular Mechanism of Regulation of Hypertension by Macro-elements (Na, K, Ca and Mg), Micro-elements/Trace Metals (Zn and Cu) and Toxic Elements (Pb and As).Biological trace element research · 2024Review
- Industrialized human gut microbiota increases CD8+ T cells and mucus thickness in humanized mouse gut.Gut microbes · 2023Article
- Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet.Nutrients · 2023Article
- New insights into the role of dietary triglyceride absorption in obesity and metabolic diseases.Frontiers in pharmacology · 2023Review
- Ingestion of whey protein and β-conglycinin exerts opposite effects on intestinal FGF15 and serotonin secretion in mice.Frontiers in endocrinology · 2023Article
- Article
- Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response.Biomedicines · 2022Article
- The AT1 Receptor Blocker Telmisartan Reduces Intestinal Mucus Thickness in Obese Mice.Frontiers in pharmacology · 2022Article
- Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice.Frontiers in physiology · 2022Article
- Spatial discordances between mRNAs and proteins in the intestinal epithelium.Nature metabolism · 2021Article
- Overexpression of Vitamin D Receptor in Intestinal Epithelia Protects Against Colitis via Upregulating Tight Junction Protein Claudin 15.Journal of Crohn's & colitis · 2021Article
- Article
- Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation.Cell host & microbe · 2021Article
- Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundObesity and insulin resistance are two major risk factors underlying the metabolic syndrome. The development of these metabolic disorders is frequently studied, but mainly in liver, skeletal muscle, and adipose tissue. To gain more insight in the role of the small intestine in development of obesity and insulin resistance, dietary fat-induced differential gene expression was determined along the longitudinal axis of small intestines of C57BL/6J mice.
methodsMale C57BL/6J mice were fed a low-fat or a high-fat diet that mimicked the fatty acid composition of a Western-style human diet. After 2, 4 and 8 weeks of diet intervention small intestines were isolated and divided in three equal parts. Differential gene expression was determined in mucosal scrapings using Mouse genome 430 2.0 arrays.
resultsThe high-fat diet significantly increased body weight and decreased oral glucose tolerance, indicating insulin resistance. Microarray analysis showed that dietary fat had the most pronounced effect on differential gene expression in the middle part of the small intestine. By overrepresentation analysis we found that the most modulated biological processes on a high-fat diet were related to lipid metabolism, cell cycle and inflammation. Our results further indicated that the nuclear receptors Ppars, Lxrs and Fxr play an important regulatory role in the response of the small intestine to the high-fat diet. Next to these more local dietary fat effects, a secretome analysis revealed differential gene expression of secreted proteins, such as Il18, Fgf15, Mif, Igfbp3 and Angptl4. Finally, we linked the fat-induced molecular changes in the small intestine to development of obesity and insulin resistance.
conclusionDuring dietary fat-induced development of obesity and insulin resistance, we found substantial changes in gene expression in the small intestine, indicating modulations of biological processes, especially related to lipid metabolism. Moreover, we found differential expression of potential signaling molecules that can provoke systemic effects in peripheral organs by influencing their metabolic homeostasis. Many of these fat-modulated genes could be linked to obesity and/or insulin resistance. Together, our data provided various leads for a causal role of the small intestine in the etiology of obesity and/or insulin resistance.
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Registered trials
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