Skip to main content

Advertisement

SpringerLink
Log in

High-Fat Diet Induces Disruption of the Tight Junction-Mediated Paracellular Barrier in the Proximal Small Intestine Before the Onset of Type 2 Diabetes and Endotoxemia

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background/Aim

A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes.

Methods/Results

HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-α levels in plasma or adipose tissue, and in intestinal segments as compared to the controls.

Conclusion

Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Gomes JM, Costa JA, Alfenas RG. Metabolic endotoxemia and diabetes mellitus: a systematic review. Metabolism. 2017;68:133–144.

    Article  CAS  PubMed  Google Scholar 

  2. Geurts L, Neyrinck AM, Delzenne NM, Knauf C, Cani PD. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics. Benef Microbes. 2014;5:3–17.

    Article  CAS  PubMed  Google Scholar 

  3. Song MJ, Kim KH, Yoon JM, Kim JB. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochem Biophys Res Commun. 2006;346:739–745.

    Article  CAS  PubMed  Google Scholar 

  4. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111–1119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9:799–809.

    Article  CAS  PubMed  Google Scholar 

  6. van der Flier LG, Clevers HC. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol. 2009;71:241–260.

    Article  CAS  PubMed  Google Scholar 

  7. Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol. 2000;279:G851–G857.

    Article  CAS  PubMed  Google Scholar 

  8. Van Itallie CM, Holmes J, Bridges A, et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci. 2008;121:298–305.

    Article  PubMed  CAS  Google Scholar 

  9. Günzel D, Fromm M. Claudins and other tight junction proteins. Compr Physiol. 2012;2:1819–1852.

    Article  PubMed  Google Scholar 

  10. Cummins PM. Occludin: one protein, many forms. Mol Cell Biol. 2012;32:242–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bauer H, Zweimueller-Mayer J, Steinbacher P, Lametschwandtner A, Bauer HC. The dual role of zonula occludens (ZO) proteins. J Biomed Biotechnol. 2010;2010:402593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rao R. Occludin phosphorylation in regulation of epithelial tight junctions. Ann N Y Acad Sci. 2009;1165:62–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Stamatovic SM, Johnson AM, Sladojevic N, Keep RF, Andjelkovic AV. Endocytosis of tight junction proteins and the regulation of degradation and recycling. Ann N Y Acad Sci. 2017;1397:54–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Butt AM, Khan IB, Hussain M, Idress M, Lu J, Tong Y. Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1, -3 and -4. Mol Biol Rep. 2012;39:1359–1369.

    Article  CAS  PubMed  Google Scholar 

  15. Utech M, Mennigen R, Bruewer M. Endocytosis and recycling of tight junction proteins in inflammation. J Biomed Biotechnol. 2010;2010:484987.

    Article  PubMed  CAS  Google Scholar 

  16. Mongelli-Sabino BM, Canuto LP, Collares-Buzato CB. Acute and chronic exposure to high levels of glucose modulates tight junction-associated epithelial barrier function in a renal tubular cell line. Life Sci. 2017;188:149–157.

    Article  CAS  PubMed  Google Scholar 

  17. Ghezzal S, Postal BG, Quevrain E, et al. Palmitic acid damages gut epithelium integrity and initiates inflammatory cytokine production. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865:158530.

    Article  CAS  PubMed  Google Scholar 

  18. Matheus VA, Monteiro LC, Oliveira RB, Maschio DA, Collares-Buzato CB. Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice. Exp Biol Med. 2017;242:1214–1226.

    Article  CAS  Google Scholar 

  19. Yuhan R, Koutsouris A, Savkovic SD, Hecht G. Enteropathogenic Escherichia coli-induced myosin light chain phosphorylation alters intestinal epithelial permeability. Gastroenterology. 1997;113:1873–1882.

    Article  CAS  PubMed  Google Scholar 

  20. Nusrat A, von Eichel-Streiber C, Turner JR, Verkade P, Madara JL, Parkos CA. Clostridium difficile toxins disrupt epithelial barrier function by altering membrane microdomain localization of tight junction proteins. Infect Immun. 2001;69:1329–1336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4:e1251384.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–1772.

    Article  CAS  PubMed  Google Scholar 

  23. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic diet–induced obesity and diabetes in mice. Diabetes. 2008;57:1470–1481.

    Article  CAS  PubMed  Google Scholar 

  24. Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016;4:525–536.

    Article  CAS  PubMed  Google Scholar 

  25. Brun P, Castagliuolo I, Di Leo V, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292:G518–G525.

    Article  CAS  PubMed  Google Scholar 

  26. Horton F, Wright J, Smith L, Hinton PJ, Robertson MD. Increased intestinal permeability to oral chromium (51 Cr) -EDTA in human Type 2 diabetes. Diabet Med. 2014;31:559–563.

    Article  CAS  PubMed  Google Scholar 

  27. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222:332–339.

    Article  Google Scholar 

  28. Oliveira RB, Matheus VA, Canuto LP, De Sant'ana A, Collares-Buzato CB. Time-dependent alteration to the tight junction structure of distal intestinal epithelia in type 2 prediabetic mice. Life Sci. 2019;238:116971.

    Article  PubMed  CAS  Google Scholar 

  29. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol. 2016;14:1–14.

    Article  CAS  Google Scholar 

  30. Oliveira RB, Canuto LP, Collares-Buzato CB. Intestinal luminal content from high-fat-fed prediabetic mice changes epithelial barrier function in vitro. Life Sci. 2019;216:10–21.

    Article  CAS  PubMed  Google Scholar 

  31. Sturgeon C, Lan J, Fasano A. Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model. Ann N Y Acad Sci. 2017;1397:130–142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Batista AV, Junior RP, Gonçalves DD, et al. Morphometric and quantitative analysis of the intestine of Rattus rattus infected by Strongyloides spp. Afr J Bacteriol Res. 2016;8:1–7.

    Google Scholar 

  33. Williams RW, von Bartheld CS, Rosen GD. Counting cells in sectioned material: a suite of techniques, tools, and tips. Curr Protoc Neurosci. 2004;24:1.11.1–1.11.29.

  34. Gulbinowicz M, Berdel B, Wójcik S, et al. Morphometric analysis of the small intestine in wild type mice C57BL/6L: a developmental study. Folia Morphol (Warsz). 2004;63:423–430.

    Google Scholar 

  35. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012;10:1096–1100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Oliveira R, Maschio DA, Carvalho CF, Collares-Buzato CB. Influence of gender and time diet exposure on endocrine pancreas remodeling in response to high fat diet-induced metabolic disturbances in mice. Ann Anat. 2015;200:88–97.

    Article  CAS  PubMed  Google Scholar 

  37. Maschio DA, Oliveira RB, Santos MR, Carvalho CF, Barbosa-Sampaio HL, Collares-Buzato CB. Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice. Biochem Biophys Res Commun. 2016;478:1534–1540.

    Article  CAS  PubMed  Google Scholar 

  38. Carvalho CF, Oliveira RB, Britan A, et al. Impaired β-cell-β-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Metab. 2012;303:E144–E151.

    CAS  Google Scholar 

  39. Oliveira RB, Carvalho CF, Polo CC, et al. Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice. Int J Exp Pathol. 2014;95:296–308.

    Article  CAS  PubMed Central  Google Scholar 

  40. Falcão VT, Maschio DA, de Fontes CC, et al. Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMs) in diabetic mice after prolonged high-fat diet. Histochem Cell Biol. 2016;146:13–31.

    Article  PubMed  CAS  Google Scholar 

  41. Shi L, Zeng M, Sun Y, Fu BM. Quantification of blood-brain barrier solute permeability and brain transport by multiphoton microscopy. J Biomech Eng. 2014;136:31005.

    Article  Google Scholar 

  42. Liang GH. Weber CR Molecular aspects of tight junction barrier function. Curr Opin Pharmacol. 2014;19:84–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Thomson A, Smart K, Somerville MS, et al. The Ussing chamber system for measuring intestinal permeability in health and disease. BMC Gastroenterol. 2019;19:98.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Watson AJ, Chu S, Sieck L, et al. Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology. 2005;129:902–912.

    Article  PubMed  Google Scholar 

  45. Du Y, Ding H, Vanarsa K, et al. Low dose epigallocatechin gallate alleviates experimental colitis by subduing inflammatory cells and cytokines, and improving intestinal permeability. Nutrients. 2019;11:1–13.

    CAS  Google Scholar 

  46. Yan Y, Kolachala V, Dalmasso G, et al. Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis. PLoS One. 2009;4:e6073.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Shan CY, Yang JH, Kong Y, et al. Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats. J Endocrinol. 2013;218:255–262.

    Article  CAS  PubMed  Google Scholar 

  48. Geboes K. Histopathology of Crohn’s disease and ulcerative colitis. In: Satsangi J, Suther-land LR, eds. Inflammatory bowel disease. 4th ed. Edinburgh: Churchill Livingstone Elsevier; 2003:255–276.

    Google Scholar 

  49. Lechuga S, Ivanov AI. Disruption of the epithelial barrier during intestinal inflammation: quest for new molecules and mechanisms. Biochim Biophys Acta Mol Cell Res. 2017;1864:1183–1194.

    Article  CAS  PubMed  Google Scholar 

  50. Kurashima Y, Goto Y, Kiyono H. Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation. Eur J Immunol. 2013;43:3108–3115.

    Article  CAS  PubMed  Google Scholar 

  51. Costa RF, Caro PL, de Matos-Neto EM, et al. Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa. J Cachexia Sarcopenia Muscle. 2019;10:1116–1127.

    Article  PubMed  PubMed Central  Google Scholar 

  52. McCauley HA, Guasch G. Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia. Trends Mol Med. 2015;21:492–503.

    Article  CAS  PubMed  Google Scholar 

  53. Saetta M, Turato G, Baraldo S, et al. Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med. 2000;161:1016–1021.

    Article  CAS  PubMed  Google Scholar 

  54. Shaw D, Gohil K, Basson MD. Intestinal mucosal atrophy and adaptation. World J Gastroenterol. 2012;18:6357–6375.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Huang C, Chen J, Wang J, et al. Dysbiosis of intestinal microbiota and decreased antimicrobial peptide level in paneth cells during hypertriglyceridemia-related acute necrotizing pancreatitis in rats. Front Microbiol. 2017;8:776.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Chalmers AD, Whitley P. Continuous endocytic recycling of tight junction proteins: how and why? Essays Biochem. 2012;53:41–54.

    Article  CAS  PubMed  Google Scholar 

  57. Inai T, Kobayashi J, Shibata Y. Claudin-1 contributes to the epithelial barrier function in MDCK cells. Eur J Cell Biol. 1999;78:849–855.

    Article  CAS  PubMed  Google Scholar 

  58. Milatz S, Krug S, Rosenthal R, et al. Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes. Biochim Biophys Acta Biomembr. 2010;1798:2048–2057.

    Article  CAS  Google Scholar 

  59. De Benedetto A, Latchney LR, McGirt LY, et al. The tight junction protein, claudin-1 is dysregulated in atopic dermatitis. J Allergy Clin Immunol. 2008;121:S32.

    Article  Google Scholar 

  60. Hashimoto K, Oshima T, Tomita T, et al. Oxidative stress induces gastric epithelial permeability through claudin-3. Biochem Biophys Res Commun. 2008;376:154–157.

    Article  CAS  PubMed  Google Scholar 

  61. Fujita H, Sugimoto K, Inatomi S, et al. Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2 + absorption between enterocytes. Mol Biol Cell. 2008;19:1912–1921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Amasheh S, Meiri N, Gitter AH, et al. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci. 2002;115:4969–4976.

    Article  CAS  PubMed  Google Scholar 

  63. Rosenthal R, Günzel D, Krug SM, Schulzke JD, Fromm M, Yu AL. Claudin-2-mediated cation and water transport share a common pore. Acta Physiol (Oxf). 2017;219:521–536.

    Article  CAS  Google Scholar 

  64. Martini E, Krug SM, Siegmund B, Neurath MF, Becker C. Mend your fences: the epithelial barrier and its relationship with mucosal immunity in inflammatory bowel disease. Cell Mol Gastroenterol Hepatol. 2017;4:33–46.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zeissig S, Bürgel N, Günzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut. 2007;56:61–72.

    Article  CAS  PubMed  Google Scholar 

  66. Umeda K, Ikenouchi J, Katahira-Tayama S, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell. 2006;126:741–754.

    Article  CAS  PubMed  Google Scholar 

  67. Stenman LK, Holma R, Korpela R. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids. World J Gastroenterol. 2012;18:923–929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Van Spaendonk H, Ceuleers H, Witters L, et al. Regulation of intestinal permeability: the role of proteases. World J Gastroenterol. 2017;23:2106–2123.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Wang H-B, Wang P-Y, Wang X, Wan Y-L, Liu Y-C. Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription. Dig Dis Sci. 2012;57:3126–3135. https://doi.org/10.1007/s10620-012-2259-4.

    Article  CAS  PubMed  Google Scholar 

  70. Li S, Qi C, Zhu H, et al. Lactobacillus reuteri improves gut barrier function and affects diurnal variation of the gut microbiota in mice fed a high-fat diet. Food Funct. 2019;10:4705–4715.

    Article  CAS  PubMed  Google Scholar 

  71. Fang W, Xue H, Chen X, Chen K, Ling W. Supplementation with sodium butyrate modulates the composition of the gut microbiota and ameliorates high-fat diet-induced obesity in mice. J Nutr. 2019;149:747–754.

    Article  PubMed  Google Scholar 

  72. Canani RB, Di Costanzo M, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17:1519–1528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Horvath A, Leber B, Feldbacher N, et al. Effects of a multispecies synbiotic on glucose metabolism, lipid marker, gut microbiome composition, gut permeability, and quality of life in diabesity: a randomized, double-blind, placebo-controlled pilot study. Eur J Nutr. 2019;. https://doi.org/10.1007/s00394-019-02135-w.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Hawkesworth S, Moore SE, Fulford AC, et al. Evidence for metabolic endotoxemia in obese and diabetic Gambian women. Nutr Diabetes. 2013;3:e83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Vergès B, Duvillard L, Lagrost L, et al. Changes in lipoprotein kinetics associated with type 2 diabetes affect the distribution of lipopolysaccharides among lipoproteins. J Clin Endocrinol Metab. 2014;99:E1245–E1253.

    Article  PubMed  CAS  Google Scholar 

  76. Zhang D, Zhang L, Zheng Y, Yue F, Russell RD, Zeng Y. Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients. Diabetes Res Clin Pract. 2014;106:312–318.

    Article  CAS  PubMed  Google Scholar 

  77. Ruder B, Atreya R, Becker C. Tumour necrosis factor alpha in intestinal homeostasis and gut related diseases. Int J Mol Sci. 2019;20:1887.

    Article  CAS  PubMed Central  Google Scholar 

  78. Al-Obaide MI, Singh R, Datta P, et al. Gut microbiota-dependent trimethylamine-n-oxide and serum biomarkers in patients with T2DM and advanced CKD. J Clin Med. 2017;6:86.

    Article  PubMed Central  CAS  Google Scholar 

  79. Demir E, Ozkan H, Seckin KD, et al. Plasma zonulin levels as a non-invasive biomarker of intestinal permeability in women with gestational Diabetes Mellitus. Biomolecules. 2019;9:24.

    Article  PubMed Central  CAS  Google Scholar 

  80. Akash M, Rehman K, Liaqat A. Tumor necrosis factor-alpha: role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2018;119:105–110.

    Article  CAS  PubMed  Google Scholar 

  81. Everard A, Geurts L, Van Roye M, Delzenne NM, Cani PD. Tetrahydro iso-alpha acids from hops improve glucose homeostasis and reduce body weight gain and metabolic endotoxemia in high-fat diet-fed mice. PLoS One. 2012;7:e33858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Valéria H. A. C. Quitete and Dr. Alexandre L. R. de Oliveira for allowing access to their laboratory facilities. We also acknowledge the National Institute of Science and Technology in Photonics Applied to Cell Biology (INCT‐INFABiC) of the University of Campinas (UNICAMP) for granting access to confocal microscopy facilities. CBCB (CNPq# 308546/2018-0) is a recipient of Research Fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). JCN was a recipient of a M.Sc. fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, grant number 001, Brazil). RBO and VAM were recipients of Ph.D. fellowships from CNPq (Brazil).

Funding

This study was supported by a grant from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant Number 2018/02118-2).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP 13083-970, Brazil

    J. C. Nascimento, V. A. Matheus, R. B. Oliveira, S. F. S. Tada & Carla B. Collares-Buzato

Authors
  1. J. C. Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. A. Matheus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. B. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. F. S. Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carla B. Collares-Buzato
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JCN participated in the study conception, conducted the experiments, analysis, and interpretation of data and drafted the manuscript. RBO, VAM, and SFST conducted the experiments and interpretation of the data. CBCB was responsible for the study conception and design of the experiments, critical analysis, and interpretation of the data, drafting, and review of the manuscript. CBCB provided funding for this work. All authors read and approved the manuscript.

Corresponding author

Correspondence to Carla B. Collares-Buzato.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Sup. 1

Morphometry of the duodenum and jejunum mucosa from C and HF groups after 60-d treatment, analyzing the villus length and width (a), as well as the gland depth and width (b). Compared to C group, villus length increased, while the villus width and gland depth decreased in the duodenum of 60d HF diet-fed mice (a). All these parameters were unchanged in the jejunum, except the jejunal gland depth that was found to be significantly reduced in HF diet-fed mice. At least 10 villi and 10 glands were analyzed per animal (C n = 5, HF n = 5 from 2 independent experiments). Bars show means ± standard error of the mean. *p < 0.05; **p < 0.0001 (Student’s t-test). (TIFF 888 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nascimento, J.C., Matheus, V.A., Oliveira, R.B. et al. High-Fat Diet Induces Disruption of the Tight Junction-Mediated Paracellular Barrier in the Proximal Small Intestine Before the Onset of Type 2 Diabetes and Endotoxemia. Dig Dis Sci 66, 3359–3374 (2021). https://doi.org/10.1007/s10620-020-06664-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06664-x

Keywords

Search

Navigation